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Molecular and phenotypic characterization of atypical Williams–Beuren syndrome
Author(s) -
Euteneuer J.,
Carvalho C.M.B.,
Kulkarni S.,
Vineyard M.,
Mark Grady R.,
Lupski J.R.,
Shinawi M.
Publication year - 2014
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12305
Subject(s) - phenotype , penetrance , genetics , williams syndrome , biology , allele , genotype , gene , copy number variation , genotype phenotype distinction , genome , neuroscience , cognition
Williams–Beuren syndrome (WBS) is a multisystemic genomic disorder typically caused by a recurrent ˜1.5–1.8 Mb deletion on 7q11.23. Atypical deletions can provide important insight into the genotype–phenotype correlations. Here, we report the phenotypic and molecular characterization of a girl with a de novo 81.8 kb deletion in the WBS critical region, which involves the ELN and LIMK1 genes only. The patient presented at 2 months of age with extensive vascular abnormalities, mild facial dysmorphism and delays in her fine motor skills. We discuss potential molecular mechanisms and the role of ELN and LIMK1 in the different phenotypic features. We compare the findings in our patient with previously reported overlapping deletions. The phenotypic variability among these patients suggests that other factors are important in the phenotype and possibly include: position effects related to copy number variation size, variations in the non‐deleted alleles, genetic modifiers elsewhere in the genome, or reduced penetrance for specific phenotypes.