title: Mutation spectrum and genotype-phenotype correlation in Cornelia de Lange syndrome.
abstract: Cornelia de Lange syndrome (CdLS) 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 CdLS has led to diagnostic improvement and expansion of the phenotype. Mutations in five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural components of cohesin, have been identified. Approximately 60% of CdLS cases are due to NIPBL mutations, 5% caused by mutations in SMC1A, RAD21, and HDAC8 and one proband was found to carry a mutation in SMC3. To date, 311 CdLS-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 CdLS mutations with a particular emphasis on their correlation to the clinical phenotype.
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Pisa, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Mannini
authors.forename: Francesco
authors.initials: F
authors.lastname: Cucco
authors.forename: Valentina
authors.initials: V
authors.lastname: Quarantotti
authors.forename: Ian D
authors.initials: ID
authors.lastname: Krantz
authors.forename: Antonio
authors.initials: A
authors.lastname: Musio
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D004268:DNA-Binding Proteins; D003635:De Lange Syndrome / Q000175:diagnosis / Q000235:genetics*; D019066:Facies; D015870:Gene Expression; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D018797:Cell Cycle Proteins; D011508:Chondroitin Sulfate Proteoglycans; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1; C487465:NIPBL protein, human; C429022:RAD21 protein, human; C492318:SMC3 protein, human
keywords: Cornelia de Lange syndrome; HDAC8; NIPBL; RAD21; SMC1A; SMC3
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