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Mutation Spectrum and Genotype–Phenotype Correlation in C ornelia de L ange Syndrome
Author(s) -
Mannini Linda,
Cucco Francesco,
Quarantotti Valentina,
Krantz Ian D.,
Musio Antonio
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22430
Subject(s) - cornelia de lange syndrome , biology , genetics , missense mutation , proband , phenotype , mutation , nonsense mutation , genetic heterogeneity , gene
Cornelia de Lange syndrome ( C d LS ) is a clinically and genetically heterogeneous developmental disorder. Clinical features include growth retardation, intellectual disability, limb defects, typical facial dysmorphism, and other systemic involvement. The increased understanding of the genetic basis of C d LS has led to diagnostic improvement and expansion of the phenotype. Mutations in five genes ( NIPBL , SMC 1 A , SMC 3 , RAD 21 , and HDAC 8 ), all regulators or structural components of cohesin, have been identified. Approximately 60% of C d LS cases are due to NIPBL mutations, 5% caused by mutations in SMC 1 A , RAD 21 , and HDAC 8 and one proband was found to carry a mutation in SMC 3 . To date, 311 C d LS ‐causing mutations are known including missense, nonsense, small deletions and insertions, splice site mutations, and genomic rearrangements. Phenotypic variability is seen both intra‐ and intergenically. This article reviews the spectrum of C d LS mutations with a particular emphasis on their correlation to the clinical phenotype.