GTS5:Ataxia-telangiectasia syndrome (ATM): Difference between revisions

(View all pending changes)

[checked revision]

[pending revision]

← Older edit Newer edit →

VisualWikitext

@@ Line 3: / Line 3: @@
 <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-stye 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>
 ==Primary Author(s)*==
-Put your text here<span style="color:#0070C0"> (''<span class="blue-text">EXAMPLE:</span>'' Jane Smith, PhD) </span>
+Emilie Lalonde, MSc, PhD, FACMG
 ==WHO Classification of Disease==
@@ Line 40: / Line 40: @@
 ==Definition/Description of Disease==
-Put your text here <span style="color:#0070C0">(''Instructions: Include a brief general clinical description, diagnostic criteria, and differential diagnosis if applicable. Include disease context relative to other WHO classification categories, i.e. describe any information relevant to the genetic aspects of the disease from all WHO classification books in which the syndrome is described.'')</span>
+- The ATM gene is located on 11q22.3 and contains 66 exons. It encodes the ATM protein, which is a key regulator of DNA damage repair and cell cycle control pathways.
+- Heterozygous pathogenic germline variants are associated with autosomal dominant ATM-related cancer predisposition, which increases susceptibility to a range of hereditary cancers, most notable breast, prostate and pancreatic cancers. ATM is considered a moderate penetrance cancer predisposition gene, with a 2-3 fold increase in breast cancer risk compared to the general population with an absolute risk of 21-24% <ref name=":0">{{Cite journal|last=Pal|first=Tuya|last2=Schon|first2=Katherine R.|last3=Astiazaran-Symonds|first3=Esteban|last4=Balmaña|first4=Judith|last5=Foulkes|first5=William D.|last6=James|first6=Paul|last7=Klugman|first7=Susan|last8=Livinski|first8=Alicia A.|last9=Mak|first9=Julie S.|date=2025-01|title=Management of individuals with heterozygous germline pathogenic variants in ATM: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)|url=https://linkinghub.elsevier.com/retrieve/pii/S1098360024001771|journal=Genetics in Medicine|language=en|volume=27|issue=1|pages=101243|doi=10.1016/j.gim.2024.101243}}</ref><ref name=":1">NCCN Guidelines Version 3.2025, Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate.</ref>. ATM has also been associated with predisposition to ovarian cancer, colorectal cancer and melanoma, but additional confirmatory studies are needed<ref name=":0" /><ref name=":1" />.
+- Biallelic pathogenic germline variants are associated with autosomal recessive ataxia telangiectasia (AT), a multisystem neurodegenerative disorder. Individuals with AT are at significantly increased risk of lymphoid malignancies in childhood or early adulthood as well as early-onset breast cancer.
+<span style="color:#0070C0">(''Instructions: Include a brief general clinical description, diagnostic criteria, and differential diagnosis if applicable. Include disease context relative to other WHO classification categories, i.e. describe any information relevant to the genetic aspects of the disease from all WHO classification books in which the syndrome is described.'')</span>
 ==Epidemiology/Prevalence==
-Put your text here
+- The incidence of heterozygous pathogenic germline variants is estimated to range from approximately 1:100 to 1:400, depending on the population<ref name=":0" />
 ==Genetic Abnormalities: Germline==
 Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Describe germline alteration(s) that cause the syndrome. In the notes, include additional details about most common mutations including founder mutations, mechanisms of molecular pathogenesis, alteration-specific prognosis and any other important genetics-related information. If multiple causes of the syndrome, include relative prevalence of genetic contributions to that syndrome. Please include references throughout the table. Do not delete the table.'')</span>