Morales et al. (2009) described 8 individuals, 6 from 2 Saudi Arabian families and 2 sporadic cases, who displayed many of the key features of Weill-Marchesani syndrome (WMS; see 277600), including lenticular myopia, ectopia lentis, glaucoma, spherophakia, and ... Morales et al. (2009) described 8 individuals, 6 from 2 Saudi Arabian families and 2 sporadic cases, who displayed many of the key features of Weill-Marchesani syndrome (WMS; see 277600), including lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. However, none of the patients had the characteristic brachydactyly or decreased joint flexibility of WMS. Radner et al. (2013) studied 4 patients from 3 consanguineous Tunisian families with features of Weill-Marchesani-like syndrome, including short stature, brachydactyly with joint stiffness, microspherophakia, ectopia lentis, and mitral valve defects, who also exhibited collodion membrane at birth that evolved to generalized ichthyosis. The patients all shared a 100-kb deletion on chromosome 15q36.3 between SNP markers dbSNP rs1080492 and dbSNP rs7179355 that encompassed the first 3 exons of the ADAMTS17 gene, the complete sequence of the noncoding RNA FLJ42289, and exon 13 of the CERS3 gene (615276), including the 3-prime UTR. Haplotype analysis in the 4 patients, who originated from the same geographic region in Tunisia, was consistent with a founder effect. Sequencing of the CERS3 gene in an unrelated Tunisian patient with isolated ichthyosis (ARCI9; 615023) revealed a splice site mutation (615276.0001), suggesting that the previously unreported skin phenotype in the patients with Weill-Marchesani-like syndrome was due to partial deletion of the CERS3 gene.
In 4 affected sibs from a consanguineous Saudi Arabian family with a Weill-Marchesani-like syndrome, Morales et al. (2009) identified homozygosity for a 1-bp insertion in the ADAMTS17 gene (607511.0001) that fully segregated with the phenotype. Screening the ADAMTS17 ... In 4 affected sibs from a consanguineous Saudi Arabian family with a Weill-Marchesani-like syndrome, Morales et al. (2009) identified homozygosity for a 1-bp insertion in the ADAMTS17 gene (607511.0001) that fully segregated with the phenotype. Screening the ADAMTS17 gene in similar WMS-like patients identified a homozygous truncating mutation (607511.0002) in 2 affected sisters from another Saudi Arabian family, and a homozygous splice site mutation in a sporadic case (607511.0003). None of the mutations were detected in 300 ethnically matched controls. A sporadic patient, a 36-year-old woman with similar features, had no mutations in ADAMTS10, ADAMTS17, or FBN1, suggesting genetic heterogeneity.