Autosomal recessive congenital cataract, intellectual disability phenotype linked to STX3 in a consanguineous Tunisian family

Abstract

The aim of this study is to investigate the genetic basis of autosomal recessive congenital cataract and intellectual disability phenotype in a consanguineous Tunisian family. The whole genome scan of the studied family was performed with single nucleotide polymorphisms (SNPs). The resulted runs of homozygosity (ROH) were analyzed through the integrated Systems Tool for Eye gene discovery (iSyTE) in order to prioritize candidate genes associated with congenital cataract. Selected genes were amplified and sequenced. Bioinformatic analysis was conducted to predict the function of the mutant gene. We identified a new specific lens gene named syntaxin 3 linked to the studied phenotype. The direct sequencing of this gene revealed a novel missense mutation c.122A>G which results in p.E41G. Bioinformatic analysis suggested a deleterious effect of this mutation on protein structure and function. Here, we report for the first time a missense mutation of a novel lens specific gene STX3 in a phenotype associating autosomal recessive congenital cataract and intellectual disability.

MYO5B,STX3, andSTXBP2mutations reveal a common disease mechanism that unifies a subset of congenital diarrheal disorders: A mutation update

“…Such data are eagerly awaited in order to understand and describe how the phenotype, impact, or onset of the disease might differ depending on the mutations. This is further emphasized by the fact that MYO5B , STX3 , and STXBP2 mutations have also been identified in patients without intestinal symptoms (Chograni et al., ; Gonzales et al., ; Pagel et al., ; Qiu et al., ) (see below). Therefore, it is important to understand how the different MYO5B, STX3 , and STXBP2 mutations and the affected residues may impact the function of the encoded proteins.…”

“…Notably, a homozygous missense STX3 mutation was also identified in a patient with autosomal recessive congenital cataract and intellectual disability phenotype without reported intestinal symptoms (Chograni et al., ). This c.122A > G mutation is predicted to lead to the substitution of a glutamic acid with a glycine at position 41 which is on the surface of the first helix of the Habc regulatory domain of syntaxin‐3 (Figure A and C).…”

Systems biology of lens development: A paradigm for disease gene discovery in the eye

“…Thus, such analysis benefits from additional biological insights through iSyTE . Indeed, several studies have successfully applied iSyTE in their investigations of eye and lens defects in human patients, namely for: 1) prioritization of novel candidate genes for pediatric cataract (Aldahmesh et al, 2012); 2) prioritization of promising candidates for anophthalmia and microphthalmia (Schilter et al, 2013); 3) linking ADAMTS18 in ocular syndrome in microcornea and myopia (Aldahmesh et al, 2013), 4) linking STX3 to congenital cataract (Chograni et al, 2014), and 5) identifying ASPH mutations that are associated with Traboulsi syndrome with ocular lens dislocation (Patel et al, 2014). Further, in 2012 iSyTE correctly predicted SIPA1l3 as a cataract-linked gene (Fig.…”

Microvillus Inclusion Disease: A Rare Mutation of STX3 in Exon 9 Causing Fatal Congenital Diarrheal Disease

“…600876). 1,[6][7][8][9]12 These include a homozygous nonsense mutation (c.739C > T, p.Arg247 à , Ensembl COSM193004) in exon 9 and a homozygous frame-shifting 2-bp insertion (c.372_373dup, p.Arg125Leufs à 7) in exon 6 of STX3. Both mutations were predicted to cause cellular STX3 protein depletion and truncation.…”