GTS5:Turner syndrome: Difference between revisions - Compendium of Cancer Genome Aberrations

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[[GTS5:Table_of_Contents|Genetic Tumour Syndromes (Who Classification, 5th ed.)]]

(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-style manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ HUGO-approved gene names and symbols] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' ''[[Author_Instructions]]'' ''and [[Frequently Asked Questions (FAQs)|FAQs]] as well as contact your [[Leadership|Associate Editor]] or [mailto:CCGA@cancergenomics.org Technical Support].)''

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Kathleen M. Bone, PhD, Medical College of Wisconsin

==WHO Classification of Disease==

{| class="wikitable"

!Structure

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|-

|Book

|Genetic ~~Tumor~~ Syndromes (5th ed.)

|Genetic Tumour Syndromes (5th ed.)

|-

|Category

|DNA repair and genomic ~~instability~~

|DNA repair and genomic stability

|-

|Family

|Chromosomal ~~and~~ non-dysjunction (aneuploidy) syndromes

|Chromosomal non-dysjunction (aneuploidy) syndromes

|-

|Type

|~~N/A~~

|Turner syndrome

|-

|Subtype(s)

|~~Turner Syndrome~~

|N/A

|}

==Related Terminology==

{| class="wikitable"

|+

|Acceptable

|45,X syndrome; Ullrich-Turner syndrome

|-

|Not Recommended

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|-

|''SHOX''||Whole or partial X chromosome loss encompassing gene||Haploinsufficiency||''De novo'', complete penetrance, complete expressivity

|The ''short stature homeobox'' (''SHOX'') gene belongs to the paired homeobox family and is located in the pseudoautosomal region 1 (PAR1) on the short arms of the X (Xp22.3) and Y (Yp11.3) chromosomes.<ref name=":3" /> It plays a crucial role in skeletal development, particularly in the growth plates of bones, where it regulates the proliferation and differentiation of chondrocytes, the cells responsible for cartilage formation. ''SHOX'' is vital for normal bone growth and stature, and pathogenic variants or deletions in this gene are associated with TS and other syndromes, including Leri-Weill dyschondrosteosis, and idiopathic short stature.<ref name=":2" /> Both males and females typically have two copies of the ''SHOX'' gene, as it escapes X chromosome inactivation.<ref name=":2" /><ref name=":4" />

|The ''short stature homeobox'' (''SHOX'') gene belongs to the paired homeobox family and is located in the pseudoautosomal region 1 (PAR1) on the short arms of the X (Xp22.3) and Y (Yp11.3) chromosomes.<ref name=":3">{{Cite journal|last=Rao|first=E.|last2=Weiss|first2=B.|last3=Fukami|first3=M.|last4=Rump|first4=A.|last5=Niesler|first5=B.|last6=Mertz|first6=A.|last7=Muroya|first7=K.|last8=Binder|first8=G.|last9=Kirsch|first9=S.|date=1997-05|title=Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome|url=https://pubmed.ncbi.nlm.nih.gov/9140395|journal=Nature Genetics|volume=16|issue=1|pages=54–63|doi=10.1038/ng0597-54|issn=1061-4036|pmid=9140395}}</ref> It plays a crucial role in skeletal development, particularly in the growth plates of bones, where it regulates the proliferation and differentiation of chondrocytes, the cells responsible for cartilage formation. ''SHOX'' is vital for normal bone growth and stature, and pathogenic variants or deletions in this gene are associated with TS and other syndromes, including Leri-Weill dyschondrosteosis, and idiopathic short stature.<ref name=":2">{{Cite journal|last=Binder|first=Gerhard|date=2011-02|title=Short stature due to SHOX deficiency: genotype, phenotype, and therapy|url=https://pubmed.ncbi.nlm.nih.gov/21325865|journal=Hormone Research in Paediatrics|volume=75|issue=2|pages=81–89|doi=10.1159/000324105|issn=1663-2826|pmid=21325865}}</ref> Both males and females typically have two copies of the ''SHOX'' gene, as it escapes X chromosome inactivation.<ref name=":2" /><ref name=":4">{{Cite journal|last=Berletch|first=Joel B.|last2=Yang|first2=Fan|last3=Xu|first3=Jun|last4=Carrel|first4=Laura|last5=Disteche|first5=Christine M.|date=2011-08|title=Genes that escape from X inactivation|url=https://pubmed.ncbi.nlm.nih.gov/21614513|journal=Human Genetics|volume=130|issue=2|pages=237–245|doi=10.1007/s00439-011-1011-z|issn=1432-1203|pmc=3136209|pmid=21614513}}</ref>

|-

|''SRY''

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In patients with TS who exhibit signs of virilization, the presence of Y chromosomal material is a significant concern, as it increases the risk for the development of gonadoblastoma, a type of germ cell tumor.<ref name=":1" /> To detect Y chromosomal material, polymerase chain reaction (PCR) is a sensitive and specific molecular method used for screening. PCR involves amplifying DNA sequences specific to the Y chromosome, such as ''SRY'' (sex-determining region Y), ''TSPY1'' (testis-specific protein Y-encoded), or other Y-specific markers.<ref name=":5" /> This technique can identify even low levels of mosaicism, which might not be detectable by conventional karyotyping or FISH. FISH can also be used to screen for SRY. When Y chromosomal material is confirmed, preventive measures, such as gonadectomy, are typically recommended to reduce the risk of malignancy.<ref name=":1" /> PCR is particularly valuable in cases where clinical findings and standard cytogenetic testing are inconclusive but there is strong clinical suspicion of Y chromosomal mosaicism. This molecular approach complements cytogenetic methods, providing a comprehensive evaluation for patients with TS and virilization.

In patients with TS who exhibit signs of virilization, the presence of Y chromosomal material is a significant concern, as it increases the risk for the development of gonadoblastoma, a type of germ cell tumor.<ref name=":1" /> To detect Y chromosomal material, polymerase chain reaction (PCR) is a sensitive and specific molecular method used for screening. PCR involves amplifying DNA sequences specific to the Y chromosome, such as ''SRY'' (sex-determining region Y), ''TSPY1'' (testis-specific protein Y-encoded), or other Y-specific markers.<ref name=":5">{{Cite journal|last=Mendes|first=J. R.|last2=Strufaldi|first2=M. W.|last3=Delcelo|first3=R.|last4=Moisés|first4=R. C.|last5=Vieira|first5=J. G.|last6=Kasamatsu|first6=T. S.|last7=Galera|first7=M. F.|last8=Andrade|first8=J. A.|last9=Verreschi|first9=I. T.|date=1999-01|title=Y-chromosome identification by PCR and gonadal histopathology in Turner's syndrome without overt Y-mosaicism|url=https://pubmed.ncbi.nlm.nih.gov/10341852|journal=Clinical Endocrinology|volume=50|issue=1|pages=19–26|doi=10.1046/j.1365-2265.1999.00607.x|issn=0300-0664|pmid=10341852}}</ref> This technique can identify even low levels of mosaicism, which might not be detectable by conventional karyotyping or FISH. FISH can also be used to screen for SRY. When Y chromosomal material is confirmed, preventive measures, such as gonadectomy, are typically recommended to reduce the risk of malignancy.<ref name=":1" /> PCR is particularly valuable in cases where clinical findings and standard cytogenetic testing are inconclusive but there is strong clinical suspicion of Y chromosomal mosaicism. This molecular approach complements cytogenetic methods, providing a comprehensive evaluation for patients with TS and virilization.

[[File:SRY in 45,X-46,XY.tif|center|thumb|Metaphase fluorescence in situ hybridization (FISH) analysis for SRY (red) and the X chromosome centromere (green) in an individual with Turner syndrome and a 45,X/46,XY karyotype.]]

[[File:Interphase SRY.tif|center|thumb|Interphase fluorescence in situ hybridization (FISH) analysis for SRY (red) and the X chromosome centromere (green) in an individual with Turner syndrome and a 45,X/46,XY karyotype.]]

==Additional Information==

~~Put your text here~~

N/A

==Links==

Put a link here or anywhere appropriate in this page (''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</~~span~~>

==References==

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[[Category:GTS5]]

[[Category:DISEASE]]

~~THIS IS WEHRE THE OLD TEMPLATE BEGINS~~

~~{{Under Construction}}~~

(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type, which is based on current knowledge within the WHO classification books and using resources such as PubMed for the latest information. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ HUGO-approved gene names and symbols] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' ''[[Author_Instructions]]'' ''and [[Frequently Asked Questions (FAQs)|FAQs]] as well as contact your [[Leadership|Associate Editor]] or [mailto:CCGA@cancergenomics.org Technical Support])''

~~==Primary Author(s)*==~~

~~Kathleen Bone, PhD, Medical College of Wisconsin~~

~~{| class="wikitable sortable"~~

|-

~~|'''Gene'''~~

~~|'''Genetic Variant or Variant Type'''~~

~~|'''Molecular Pathogenesis'''~~

~~|'''Inheritance, Penetrance, Expressivity'''~~

~~|'''Notes'''~~

|-

~~|''SHOX''~~

~~|Whole or partial X chromosome loss encompassing gene~~

~~|Haploinsufficiency~~

~~|''De novo'', complete penetrance, complete expressivity~~

|The ''short stature homeobox'' (''SHOX'') gene belongs to the paired homeobox family and is located in the pseudoautosomal region 1 (PAR1) on the short arms of the X (Xp22.3) and Y (Yp11.3) chromosomes.<ref name=":3">{{Cite journal|last=Rao|first=E.|last2=Weiss|first2=B.|last3=Fukami|first3=M.|last4=Rump|first4=A.|last5=Niesler|first5=B.|last6=Mertz|first6=A.|last7=Muroya|first7=K.|last8=Binder|first8=G.|last9=Kirsch|first9=S.|date=1997-05|title=Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome|url=https://pubmed.ncbi.nlm.nih.gov/9140395|journal=Nature Genetics|volume=16|issue=1|pages=54–63|doi=10.1038/ng0597-54|issn=1061-4036|pmid=9140395}}</ref> It plays a crucial role in skeletal development, particularly in the growth plates of bones, where it regulates the proliferation and differentiation of chondrocytes, the cells responsible for cartilage formation. ''SHOX'' is vital for normal bone growth and stature, and pathogenic variants or deletions in this gene are associated with TS and other syndromes, including Leri-Weill dyschondrosteosis, and idiopathic short stature.<ref name=":2">{{Cite journal|last=Binder|first=Gerhard|date=2011-02|title=Short stature due to SHOX deficiency: genotype, phenotype, and therapy|url=https://pubmed.ncbi.nlm.nih.gov/21325865|journal=Hormone Research in Paediatrics|volume=75|issue=2|pages=81–89|doi=10.1159/000324105|issn=1663-2826|pmid=21325865}}</ref> Both males and females typically have two copies of the ''SHOX'' gene, as it escapes X chromosome inactivation.<ref name=":2" /><ref name=":4">{{Cite journal|last=Berletch|first=Joel B.|last2=Yang|first2=Fan|last3=Xu|first3=Jun|last4=Carrel|first4=Laura|last5=Disteche|first5=Christine M.|date=2011-08|title=Genes that escape from X inactivation|url=https://pubmed.ncbi.nlm.nih.gov/21614513|journal=Human Genetics|volume=130|issue=2|pages=237–245|doi=10.1007/s00439-011-1011-z|issn=1432-1203|pmc=3136209|pmid=21614513}}</ref>

|}

~~==Genetic Abnormalities: Somatic==~~

~~N/A~~

~~{| class="wikitable sortable"~~

|-

~~|'''Gene'''~~

~~|'''Genetic Variant or Variant Type'''~~

~~|'''Molecular Pathogenesis'''~~

~~|'''Inheritance, Penetrance, Expressivity'''~~

~~|'''Notes'''~~

|-

~~|N/A~~

|}

~~==Genes and Main Pathways Involved==~~

~~Put your text here and fill in the table (''Instructions: Can include references in the table. Do not delete table.'')~~

~~{| class="wikitable sortable"~~

|-

~~!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome~~

|-

~~|EXAMPLE: ''BRAF'' and ''MAP2K1''; Activating mutations~~

~~|EXAMPLE: MAPK signaling~~

~~|EXAMPLE: Increased cell growth and proliferation~~

|-

~~|EXAMPLE: ''CDKN2A''; Inactivating mutations~~

~~|EXAMPLE: Cell cycle regulation~~

~~|EXAMPLE: Unregulated cell division~~

|-

~~|EXAMPLE: ''KMT2C'' and ''ARID1A''; Inactivating mutations~~

~~|EXAMPLE: Histone modification, chromatin remodeling~~

~~|EXAMPLE: Abnormal gene expression program~~

|}

~~==Genetic Diagnostic Testing Methods==~~

TS can be diagnosed prenatally through chorionic villus sampling (CVS) or amniocentesis, followed by G-banded chromosome analysis or karyotyping. Postnatal confirmation requires chromosome analysis of a phytohemagglutinin (PHA)-stimulated peripheral blood (PB) specimen. In cases of mosaicism, the karyotype may appear normal, so additional diagnostic methods may be necessary.

If TS is strongly suspected, a fluorescence in situ hybridization (FISH) study using an X chromosome centromere probe may be performed alongside karyotyping. Furthermore, if clinical suspicion remains high despite normal results from chromosome analysis and FISH, a chromosome analysis of a skin fibroblast culture may be indicated.

In patients with TS who exhibit signs of virilization, the presence of Y chromosomal material is a significant concern, as it increases the risk for the development of gonadoblastoma, a type of germ cell tumor.<ref name=":1" /> To detect Y chromosomal material, polymerase chain reaction (PCR) is a sensitive and specific molecular method used for screening. PCR involves amplifying DNA sequences specific to the Y chromosome, such as SRY (sex-determining region Y), TSPY (testis-specific protein Y-encoded), or other Y-specific markers.<ref name=":5">{{Cite journal|last=Mendes|first=J. R.|last2=Strufaldi|first2=M. W.|last3=Delcelo|first3=R.|last4=Moisés|first4=R. C.|last5=Vieira|first5=J. G.|last6=Kasamatsu|first6=T. S.|last7=Galera|first7=M. F.|last8=Andrade|first8=J. A.|last9=Verreschi|first9=I. T.|date=1999-01|title=Y-chromosome identification by PCR and gonadal histopathology in Turner's syndrome without overt Y-mosaicism|url=https://pubmed.ncbi.nlm.nih.gov/10341852|journal=Clinical Endocrinology|volume=50|issue=1|pages=19–26|doi=10.1046/j.1365-2265.1999.00607.x|issn=0300-0664|pmid=10341852}}</ref> This technique can identify even low levels of mosaicism, which might not be detectable by conventional karyotyping or FISH. When Y chromosomal material is confirmed, preventive measures, such as gonadectomy, are typically recommended to reduce the risk of malignancy.<ref name=":1" /> PCR is particularly valuable in cases where clinical findings and standard cytogenetic testing are inconclusive but there is strong clinical suspicion of Y chromosomal mosaicism. This molecular approach complements cytogenetic methods, providing a comprehensive evaluation for patients with TS and virilization.

~~==Additional Information==~~

~~Put your text here~~

~~==Links==~~

Put a link here or anywhere appropriate in this page (''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')

~~==References==~~

<references />(use the "Cite" icon at the top of the page) (''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''''.'')

~~==Notes==~~

<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''Associate Editor'']] or other CCGA representative. When pages have a major update by a new author, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author. Additional global feedback or concerns are also welcome.

~~Prior Author(s):~~

@@ Line 1: / Line 1: @@
+[[GTS5:Table_of_Contents|Genetic Tumour Syndromes (Who Classification, 5th ed.)]]
 {{Under Construction}}
 <span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-style manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>
@@ Line 4: / Line 5: @@
 Kathleen M. Bone, PhD, Medical College of Wisconsin
 ==WHO Classification of Disease==
 {| class="wikitable"
 !Structure
@@ Line 9: / Line 11: @@
 |-
 |Book
-|Genetic Tumor Syndromes (5th ed.)
+|Genetic Tumour Syndromes (5th ed.)
 |-
 |Category
-|DNA repair and genomic instability
+|DNA repair and genomic stability
 |-
 |Family
-|Chromosomal and non-dysjunction (aneuploidy) syndromes
+|Chromosomal non-dysjunction (aneuploidy) syndromes
 |-
 |Type
-|N/A
+|Turner syndrome
 |-
 |Subtype(s)
-|Turner Syndrome
+|N/A
 |}
 ==Related Terminology==
 {| class="wikitable"
 |+
 |Acceptable
 |45,X syndrome; Ullrich-Turner syndrome
 |-
 |Not Recommended
@@ Line 54: / Line 58: @@
 |-
 |''SHOX''||Whole or partial X chromosome loss encompassing gene||Haploinsufficiency||''De novo'', complete penetrance, complete expressivity
-|The ''short stature homeobox'' (''SHOX'') gene belongs to the paired homeobox family and is located in the pseudoautosomal region 1 (PAR1) on the short arms of the X (Xp22.3) and Y (Yp11.3) chromosomes.<ref name=":3" /> It plays a crucial role in skeletal development, particularly in the growth plates of bones, where it regulates the proliferation and differentiation of chondrocytes, the cells responsible for cartilage formation. ''SHOX'' is vital for normal bone growth and stature, and pathogenic variants or deletions in this gene are associated with TS and other syndromes, including Leri-Weill dyschondrosteosis, and idiopathic short stature.<ref name=":2" /> Both males and females typically have two copies of the ''SHOX'' gene, as it escapes X chromosome inactivation.<ref name=":2" /><ref name=":4" />
+|The ''short stature homeobox'' (''SHOX'') gene belongs to the paired homeobox family and is located in the pseudoautosomal region 1 (PAR1) on the short arms of the X (Xp22.3) and Y (Yp11.3) chromosomes.<ref name=":3">{{Cite journal|last=Rao|first=E.|last2=Weiss|first2=B.|last3=Fukami|first3=M.|last4=Rump|first4=A.|last5=Niesler|first5=B.|last6=Mertz|first6=A.|last7=Muroya|first7=K.|last8=Binder|first8=G.|last9=Kirsch|first9=S.|date=1997-05|title=Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome|url=https://pubmed.ncbi.nlm.nih.gov/9140395|journal=Nature Genetics|volume=16|issue=1|pages=54–63|doi=10.1038/ng0597-54|issn=1061-4036|pmid=9140395}}</ref> It plays a crucial role in skeletal development, particularly in the growth plates of bones, where it regulates the proliferation and differentiation of chondrocytes, the cells responsible for cartilage formation. ''SHOX'' is vital for normal bone growth and stature, and pathogenic variants or deletions in this gene are associated with TS and other syndromes, including Leri-Weill dyschondrosteosis, and idiopathic short stature.<ref name=":2">{{Cite journal|last=Binder|first=Gerhard|date=2011-02|title=Short stature due to SHOX deficiency: genotype, phenotype, and therapy|url=https://pubmed.ncbi.nlm.nih.gov/21325865|journal=Hormone Research in Paediatrics|volume=75|issue=2|pages=81–89|doi=10.1159/000324105|issn=1663-2826|pmid=21325865}}</ref> Both males and females typically have two copies of the ''SHOX'' gene, as it escapes X chromosome inactivation.<ref name=":2" /><ref name=":4">{{Cite journal|last=Berletch|first=Joel B.|last2=Yang|first2=Fan|last3=Xu|first3=Jun|last4=Carrel|first4=Laura|last5=Disteche|first5=Christine M.|date=2011-08|title=Genes that escape from X inactivation|url=https://pubmed.ncbi.nlm.nih.gov/21614513|journal=Human Genetics|volume=130|issue=2|pages=237–245|doi=10.1007/s00439-011-1011-z|issn=1432-1203|pmc=3136209|pmid=21614513}}</ref>
 |-
 |''SRY''
@@ Line 88: / Line 92: @@
-In patients with TS who exhibit signs of virilization, the presence of Y chromosomal material is a significant concern, as it increases the risk for the development of gonadoblastoma, a type of germ cell tumor.<ref name=":1" /> To detect Y chromosomal material, polymerase chain reaction (PCR) is a sensitive and specific molecular method used for screening. PCR involves amplifying DNA sequences specific to the Y chromosome, such as ''SRY'' (sex-determining region Y), ''TSPY1'' (testis-specific protein Y-encoded), or other Y-specific markers.<ref name=":5" /> This technique can identify even low levels of mosaicism, which might not be detectable by conventional karyotyping or FISH. FISH can also be used to screen for SRY. When Y chromosomal material is confirmed, preventive measures, such as gonadectomy, are typically recommended to reduce the risk of malignancy.<ref name=":1" /> PCR is particularly valuable in cases where clinical findings and standard cytogenetic testing are inconclusive but there is strong clinical suspicion of Y chromosomal mosaicism. This molecular approach complements cytogenetic methods, providing a comprehensive evaluation for patients with TS and virilization.
+In patients with TS who exhibit signs of virilization, the presence of Y chromosomal material is a significant concern, as it increases the risk for the development of gonadoblastoma, a type of germ cell tumor.<ref name=":1" /> To detect Y chromosomal material, polymerase chain reaction (PCR) is a sensitive and specific molecular method used for screening. PCR involves amplifying DNA sequences specific to the Y chromosome, such as ''SRY'' (sex-determining region Y), ''TSPY1'' (testis-specific protein Y-encoded), or other Y-specific markers.<ref name=":5">{{Cite journal|last=Mendes|first=J. R.|last2=Strufaldi|first2=M. W.|last3=Delcelo|first3=R.|last4=Moisés|first4=R. C.|last5=Vieira|first5=J. G.|last6=Kasamatsu|first6=T. S.|last7=Galera|first7=M. F.|last8=Andrade|first8=J. A.|last9=Verreschi|first9=I. T.|date=1999-01|title=Y-chromosome identification by PCR and gonadal histopathology in Turner's syndrome without overt Y-mosaicism|url=https://pubmed.ncbi.nlm.nih.gov/10341852|journal=Clinical Endocrinology|volume=50|issue=1|pages=19–26|doi=10.1046/j.1365-2265.1999.00607.x|issn=0300-0664|pmid=10341852}}</ref> This technique can identify even low levels of mosaicism, which might not be detectable by conventional karyotyping or FISH. FISH can also be used to screen for SRY. When Y chromosomal material is confirmed, preventive measures, such as gonadectomy, are typically recommended to reduce the risk of malignancy.<ref name=":1" /> PCR is particularly valuable in cases where clinical findings and standard cytogenetic testing are inconclusive but there is strong clinical suspicion of Y chromosomal mosaicism. This molecular approach complements cytogenetic methods, providing a comprehensive evaluation for patients with TS and virilization.
 [[File:SRY in 45,X-46,XY.tif|center|thumb|Metaphase fluorescence in situ hybridization (FISH) analysis for SRY (red) and the X chromosome centromere (green) in an individual with Turner syndrome and a 45,X/46,XY karyotype.]]
 [[File:Interphase SRY.tif|center|thumb|Interphase fluorescence in situ hybridization (FISH) analysis for SRY (red) and the X chromosome centromere (green) in an individual with Turner syndrome and a 45,X/46,XY karyotype.]]
 <br />
 ==Additional Information==
-Put your text here
+N/A
 ==Links==
-Put a link here or anywhere appropriate in this page <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
+<br />
 ==References==
 <references />
@@ Line 104: / Line 108: @@
 [[Category:GTS5]]
 [[Category:DISEASE]]
-THIS IS WEHRE THE OLD TEMPLATE BEGINS
-{{Under Construction}}
-<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type, which is based on current knowledge within the WHO classification books and using resources such as PubMed for the latest information. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])''</span>
-==Primary Author(s)*==
-Kathleen Bone, PhD, Medical College of Wisconsin
-{| class="wikitable sortable"
-|-
-|'''Gene'''
-|'''Genetic Variant or Variant Type'''
-|'''Molecular Pathogenesis'''
-|'''Inheritance, Penetrance, Expressivity'''
-|'''Notes'''
-|-
-|''SHOX''
-|Whole or partial X chromosome loss encompassing gene
-|Haploinsufficiency
-|''De novo'', complete penetrance, complete expressivity
-|The ''short stature homeobox'' (''SHOX'') gene belongs to the paired homeobox family and is located in the pseudoautosomal region 1 (PAR1) on the short arms of the X (Xp22.3) and Y (Yp11.3) chromosomes.<ref name=":3">{{Cite journal|last=Rao|first=E.|last2=Weiss|first2=B.|last3=Fukami|first3=M.|last4=Rump|first4=A.|last5=Niesler|first5=B.|last6=Mertz|first6=A.|last7=Muroya|first7=K.|last8=Binder|first8=G.|last9=Kirsch|first9=S.|date=1997-05|title=Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome|url=https://pubmed.ncbi.nlm.nih.gov/9140395|journal=Nature Genetics|volume=16|issue=1|pages=54–63|doi=10.1038/ng0597-54|issn=1061-4036|pmid=9140395}}</ref> It plays a crucial role in skeletal development, particularly in the growth plates of bones, where it regulates the proliferation and differentiation of chondrocytes, the cells responsible for cartilage formation. ''SHOX'' is vital for normal bone growth and stature, and pathogenic variants or deletions in this gene are associated with TS and other syndromes, including Leri-Weill dyschondrosteosis, and idiopathic short stature.<ref name=":2">{{Cite journal|last=Binder|first=Gerhard|date=2011-02|title=Short stature due to SHOX deficiency: genotype, phenotype, and therapy|url=https://pubmed.ncbi.nlm.nih.gov/21325865|journal=Hormone Research in Paediatrics|volume=75|issue=2|pages=81–89|doi=10.1159/000324105|issn=1663-2826|pmid=21325865}}</ref> Both males and females typically have two copies of the ''SHOX'' gene, as it escapes X chromosome inactivation.<ref name=":2" /><ref name=":4">{{Cite journal|last=Berletch|first=Joel B.|last2=Yang|first2=Fan|last3=Xu|first3=Jun|last4=Carrel|first4=Laura|last5=Disteche|first5=Christine M.|date=2011-08|title=Genes that escape from X inactivation|url=https://pubmed.ncbi.nlm.nih.gov/21614513|journal=Human Genetics|volume=130|issue=2|pages=237–245|doi=10.1007/s00439-011-1011-z|issn=1432-1203|pmc=3136209|pmid=21614513}}</ref>
-|}
-==Genetic Abnormalities: Somatic==
-N/A
-{| class="wikitable sortable"
-|-
-|'''Gene'''
-|'''Genetic Variant or Variant Type'''
-|'''Molecular Pathogenesis'''
-|'''Inheritance, Penetrance, Expressivity'''
-|'''Notes'''
-|-
-|N/A
-|N/A
-|N/A
-|N/A
-|N/A
-|}
-==Genes and Main Pathways Involved==
-Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span>
-{| class="wikitable sortable"
-|-
-!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
-|-
-|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
-|<span class="blue-text">EXAMPLE:</span> MAPK signaling
-|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
-|-
-|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
-|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
-|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
-|-
-|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
-|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
-|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
-|}
-==Genetic Diagnostic Testing Methods==
-TS can be diagnosed prenatally through chorionic villus sampling (CVS) or amniocentesis, followed by G-banded chromosome analysis or karyotyping. Postnatal confirmation requires chromosome analysis of a phytohemagglutinin (PHA)-stimulated peripheral blood (PB) specimen. In cases of mosaicism, the karyotype may appear normal, so additional diagnostic methods may be necessary.
-If TS is strongly suspected, a fluorescence in situ hybridization (FISH) study using an X chromosome centromere probe may be performed alongside karyotyping. Furthermore, if clinical suspicion remains high despite normal results from chromosome analysis and FISH, a chromosome analysis of a skin fibroblast culture may be indicated.
-In patients with TS who exhibit signs of virilization, the presence of Y chromosomal material is a significant concern, as it increases the risk for the development of gonadoblastoma, a type of germ cell tumor.<ref name=":1" /> To detect Y chromosomal material, polymerase chain reaction (PCR) is a sensitive and specific molecular method used for screening. PCR involves amplifying DNA sequences specific to the Y chromosome, such as SRY (sex-determining region Y), TSPY (testis-specific protein Y-encoded), or other Y-specific markers.<ref name=":5">{{Cite journal|last=Mendes|first=J. R.|last2=Strufaldi|first2=M. W.|last3=Delcelo|first3=R.|last4=Moisés|first4=R. C.|last5=Vieira|first5=J. G.|last6=Kasamatsu|first6=T. S.|last7=Galera|first7=M. F.|last8=Andrade|first8=J. A.|last9=Verreschi|first9=I. T.|date=1999-01|title=Y-chromosome identification by PCR and gonadal histopathology in Turner's syndrome without overt Y-mosaicism|url=https://pubmed.ncbi.nlm.nih.gov/10341852|journal=Clinical Endocrinology|volume=50|issue=1|pages=19–26|doi=10.1046/j.1365-2265.1999.00607.x|issn=0300-0664|pmid=10341852}}</ref> This technique can identify even low levels of mosaicism, which might not be detectable by conventional karyotyping or FISH. When Y chromosomal material is confirmed, preventive measures, such as gonadectomy, are typically recommended to reduce the risk of malignancy.<ref name=":1" /> PCR is particularly valuable in cases where clinical findings and standard cytogenetic testing are inconclusive but there is strong clinical suspicion of Y chromosomal mosaicism. This molecular approach complements cytogenetic methods, providing a comprehensive evaluation for patients with TS and virilization.
-==Additional Information==
-Put your text here
-==Links==
-Put a link here or anywhere appropriate in this page <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
-==References==
-<references />(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span>
-==Notes==
-<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''Associate Editor'']] or other CCGA representative.  When pages have a major update by a new author, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.  Additional global feedback or concerns are also welcome.
-Prior Author(s):