XXXX and @entity393 : More than just a modifier.

@entity32808 @entity71689 @entity68400 @entity3491 @entity2319 @entity71691 @entity71687 @entity71686 @entity74 @entity71690 @entity24129 @entity393 @entity71688
UNASSIGNED: @entity2319 is the most frequent @entity74 . With over 90 genes and 110 loci causally implicated in @entity3491 , it is phenotypically and genetically heterogeneous. Here, we investigate the genetic etiology of @entity2319 in four families of Iranian origin segregating @entity3491 ( @entity3491 ). We used a combination of linkage analysis, homozygosity mapping, and a targeted genomic enrichment platform to simultaneously screen 90 known @entity2319 -causing genes for pathogenic variants. Variant segregation was confirmed by Sanger sequencing. Linkage analysis and homozygosity mapping showed segregation with the @entity71686 locus on chromosome 10 in two families. Targeted genomic enrichment with massively parallel sequencing identified causal variants in @entity68400 : a homozygous missense variant ( @entity71687 ) in one family and compound heterozygosity for missense ( @entity71688 ) and nonsense ( @entity71689 ) variants in the second family. Screening of two additional families identified two more variants: ( @entity71690 ) and ( @entity71691 ). Variant segregation with the @entity393 phenotype was confirmed in all families by Sanger sequencing. The missense variants are predicted to be deleterious, and the two nonsense mutations produce null alleles. This report is the first to show that mutations in @entity68400 cause @entity3491 , a finding that offers addition insight into the @entity24129 interactome. We also describe a novel likely disease-causing mutation in @entity32808 and illustrate the complexity associated with gene identification in diseases that exhibit large genetic and phenotypic heterogeneity.    2015 Wiley Periodicals, Inc.
