title: Long interspersed nuclear element-1 (LINE1)-mediated deletion of EVC, EVC2, C4orf6, and STK32B in Ellis-van Creveld syndrome with borderline intelligence.
abstract: 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.
authors.affiliation: Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
authors.forename: Samia A
authors.initials: SA
authors.lastname: Temtamy
authors.forename: Mona S
authors.initials: MS
authors.lastname: Aglan
authors.forename: Maria
authors.initials: M
authors.lastname: Valencia
authors.forename: Guido
authors.initials: G
authors.lastname: Cocchi
authors.forename: Maria
authors.initials: M
authors.lastname: Pacheco
authors.forename: Adel M
authors.initials: AM
authors.lastname: Ashour
authors.forename: Khalda S
authors.initials: KS
authors.lastname: Amr
authors.forename: Sanaa M H
authors.initials: SM
authors.lastname: Helmy
authors.forename: Mona A
authors.initials: MA
authors.lastname: El-Gammal
authors.forename: Michael
authors.initials: M
authors.lastname: Wright
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
authors.forename: Judith A
authors.initials: JA
authors.lastname: Goodship
authors.forename: Victor L
authors.initials: VL
authors.lastname: Ruiz-Perez
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004613:Ellis-Van Creveld Syndrome / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D015894:Genome, Human; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D020084:Long Interspersed Nucleotide Elements / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D011506:Proteins / Q000235:genetics
chemical_list: C406058:EVC protein, human; C473310:EVC2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins