Exome sequencing revealed a novel biallelic deletion in the DCAF17 gene underlying Woodhouse Sakati syndrome.

Woodhouse Sakati syndrome (WSS, MIM 241080) is a rare autosomal recessive genetic condition characterized by alopecia, hypogonadism, hearing impairment, diabetes mellitus, learning disabilities and extrapydamidal manifestations. Sequence variants in the gene DCAF17, encoding nucleolar substrate receptor, were identified as the underlying cause of inherited WSS. Considerable phenotypic heterogeneity exists in WSS with regard to severity, organs involvement and age of onset, both in inter-familial and intra-familial cases. In this study, the genetic characterization of a consanguineous pedigree showing mild features of WSS was performed, followed by structural analysis of truncated protein. Exome sequencing identified a novel single base deletion variant (c.270delA; K90Nfs8*) in third exon of the gene DCAF17 (RefSeq; NM_025000), resulting in a truncated protein. Structural analysis of truncated DCAF17 revealed absence of amino acid residues crucial for interaction with DDB1. Taken together, the data confirmed the single base pair deletion as the underlying cause of this second report of WSS from Pakistan. This signifies the vital yet unexplored role of DCAF17 both in development and maintenance of adult tissues homeostasis.

Next generation sequencing to determine the cystic fibrosis mutation spectrum in Palestinian population.

An extensive molecular analysis of the CF transmembrane regulator (CFTR) gene was performed to establish the CFTR mutation spectrum and frequencies in the Palestinian population, which can be considered as an understudied population. We used a targeted Next Generation Sequencing approach to sequence the entire coding region and the adjacent sequences of the CFTR gene combined with MLPA analysis of 60 unrelated CF patients. Eighteen different CF-causing mutations, including one previously undescribed mutation p.(Gly1265Arg), were identified. The overall detection rate is up to 67%, and when we consider only CF patients with sweat chloride concentrations >70 mEq/L, we even have a pickup rate of 92%. Whereas p.(Phe508del) is the most frequent allele (35% of the positive cases), 3 other mutations c.2988+1Kbdel8.6Kb, c.1393-1G>A, and p.(Gly85Glu) showed frequencies higher than 5% and a total of 9 mutations account for 84% of the mutations. This limited spectrum of CF mutations is in agreement with the homozygous ethnic origin of the Palestinian population. The relative large portion of patients without a mutation is most likely due to clinical misdiagnosis. Our results will be important in the development of an adequate molecular diagnostic test for CF in Palestine.