Clinical and Molecular Characterization of a RASopathy Cohort From Türkiye and an AMMECR1-Related Noonan Syndrome-Mimicking Phenotype
CLINICAL GENETICS, cilt.110, sa.4, ss.471-479, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 110 Sayı: 4
- Basım Tarihi: 2026
- Doi Numarası: 10.1111/cge.70217
- Dergi Adı: CLINICAL GENETICS
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Sayfa Sayıları: ss.471-479
- Anahtar Kelimeler: AMMECR1, exome sequencing, MFHIEN, Noonan syndrome, RAS/MAPK pathway, RASopathy
- İstanbul Üniversitesi Adresli: Evet
Özet
RASopathies comprise a group of congenital malformation syndromes with predominant neuro-cardio-facial-cutaneous involvement resulting from pathogenic variants in RAS/mitogen-activated protein kinase (MAPK) signaling pathway genes. In this study 33 patients are presented with their clinical and molecular findings as an RASopathy cohort including a family with an AMMECR1-related disorder. The diagnostic distribution of the cohort included Noonan syndrome (n = 18), neurofibromatosis type 1 (n = 8), and single cases of cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis-Noonan syndrome, NF1 microdeletion syndrome, Noonan syndrome-like disorder with loose anagen hair, Noonan syndrome with multiple lentigines and AMMECR1-related midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis (MIM# 300990). The most prevalent clinical manifestations were dermatological findings (90.9%), skeletal features (84.4%), cardiovascular involvement (75.8%), and typical craniofacial dysmorphism suggestive of RASopathy (72.7%). Variants were most frequently identified in PTPN11 and NF1, followed by single cases involving the BRAF, HRAS, LZTR1, RAF1, RIT1, SHOC2, and SOS1. Notably, one patient harbored a variant in AMMECR1, which is not involved in the RAS/MAPK pathway. Overall, this study delineates the clinical and molecular landscape of a cohort from T & uuml;rkiye and underscores that the AMMECR1-related phenotype represents a distinct entity that closely mimics Noonan syndrome.