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Genotype–phenotype correlations in Cornelia de Lange syndrome: Behavioral characteristics and changes with age
Author(s) -
Moss Joanna,
Penhallow Jessica,
Ansari Morad,
Barton Stephanie,
Bourn David,
FitzPatrick David R.,
Goodship Judith,
Hammond Peter,
Roberts Catherine,
Welham Alice,
Oliver Chris
Publication year - 2017
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38228
Subject(s) - cornelia de lange syndrome , intellectual disability , autism , genetics , cohesin , impulsivity , mood , autism spectrum disorder , mutation , phenotype , genotype , genetic heterogeneity , psychology , biology , gene , clinical psychology , developmental psychology , chromosome
Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder associated with unusual facial features, limb abnormalities, a wide range of health conditions, and intellectual disability. Mutations in five genes that encode ( SMC1A , SMC3 , RAD21 ) or regulate ( NIPBL , HDAC8 ) the cohesin complex have been identified in up to 70% of individuals. Genetic cause remains unknown for a proportion of individuals. There is substantial heterogeneity in all aspects of CdLS but very little is known about what predicts phenotypic heterogeneity. In this study, we evaluated genotype–phenotype associations in 34 individuals with CdLS. Participants with NIPBL mutations had significantly lower self help skills and were less likely to have verbal skills relative to those who were negative for the NIPBL mutation. No significant differences were identified between the groups in relation to repetitive behavior, mood, interest and pleasure, challenging behavior, activity, impulsivity, and characteristics of autism spectrum disorder whilst controlling differences in self help skills. Significant correlations indicating lower mood, interest and pleasure, and increased insistence on sameness with older age were identified for those who were NIPBL mutation positive. The findings suggest similarities in the behavioral phenotype between those with and without the NIPBL mutation once differences in self help skills are controlled for. However, there may be subtle differences in the developmental trajectory of these behaviors according to genetic mutation status in CdLS.