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Long interspersed nuclear element‐1 (LINE1)‐mediated deletion of EVC , EVC2 , C4orf6 , and STK32B in Ellis–van Creveld syndrome with borderline intelligence
Author(s) -
Temtamy Samia A.,
Aglan Mona S.,
Valencia Maria,
Cocchi Guido,
Pacheco Maria,
Ashour Adel M.,
Amr Khalda S.,
Helmy Sanaa M.H.,
ElGammal Mona A.,
Wright Michael,
Lapunzina Pablo,
Goodship Judith A.,
RuizPerez Victor L.
Publication year - 2008
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.20778
Subject(s) - genetics , biology , allele , compound heterozygosity , gene , phenotype , heterozygote advantage , recombination , autosomal recessive inheritance , mutation
Previous work has shown Ellis–van Creveld (EvC) patients with mutations either in both alleles of EVC or in both alleles of EVC2 . We now report affected individuals with the two genes inactivated on each allele. In a consanguineous pedigree diagnosed with EvC and borderline intelligence, we detected a 520‐kb homozygous deletion comprising EVC, EVC2, C4orf6 , and STK32B , caused by recombination between long interspersed nuclear element‐1 (LINE‐1 or L1) elements. Patients homozygous for the deletion are deficient in EVC and EVC2 and have no increase in the severity of the EvC typical features. Similarly deletion carriers demonstrate absence of digenic inheritance in EvC. Further, the phenotype of these patients suggests that the EVC‐STK32B deletion also leads to mild mental retardation and reveals that loss of the novel genes C4orf6 and STK32B causes at most mild mental deficit. In an EvC compound heterozygote of different ethnic origin we identified the same LINE‐to‐LINE rearrangement due to a different recombination event. These findings highlight the importance of L1 repetitive sequences in human genome architecture and disease. Hum Mutat 29(7), 931–938, 2008. © 2008 Wiley‐Liss, Inc.