Unraveling the Genetic Puzzle: Could MAP3K7 Be a Candidate Gene for RASopathies? Case Presentation

• Published in: Journal of clinical research in pediatric endocrinology
• Main Authors: Kizilcan Cetin, Sirmen, Siklar, Zeynep, Aycan, Zehra, Ozsu, Elif, Ceylaner, Serdar, Berberoğlu, Merih
• Format: Journal Article
• Language: English
• Published: Turkey 17-10-2024
• Subjects: Noonan Syndrome; short stature; MAP3K7
• ISSN: 1308-5727; 1308-5735; 1308-5735
• DOI: 10.4274/jcrpe.galenos.2024.2024-3-5

Noonan Syndrome (NS) diagnosis is challenging due to diverse clinical manifestations. Here, our case report highlights
's novel role in NS. A 10.4-year-old female patient presented with short stature and suggestive clinical findings of RASopathy. Despite atypical facial features, the patient met two major diagnostic criteria of Van der Burgt.Initial genetic testing for known NS-associated genes did not find any variants. Later, whole exome sequencing (WES) discovered a unique de novo heterozygous variant (c.65C>A, p.(P22H)) in the
. This variant, categorized as a variant of uncertain significance (VUS) by the American College of Medical Genetics and Genomics (ACMG) criteria, raised questions about its potential role in NS. The patient's clinical presentation deviated from classical manifestations of
-associated syndromes, underscoring the genetic and molecular mechanisms' complexity. Notably, this is the first case reported to associate
variants with NS, advancing knowledge of the condition's genetic causes. Despite challenges in NS diagnosis, proper management, including recombinant growth hormone therapy, is crucial for optimizing growth potential. The case underscores
as a potential candidate gene for NS, and more functional genetic investigations are required to clarify the delicate interaction between genetic abnormalities, the RAS/MAPK pathway, and clinical manifestations observed in NS cases.