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.

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Our study identified a new gene to be included in the large spectrum of cataract-associated genes. Importantly, the study demonstrated that, in addition to lens-enriched genes that exhibit high expression levels, genes identified by iSyTE that are highly lens-enriched but have lower absolute expression may also represent candidates for potential function in the lens.

The aim of this study was to identify the genetic defect that is responsible for aniridia and congenital cataracts in two Tunisian families. Sequencing of the PAX6 gene in family F1 detected a novel c.265C4T transition in exon 6. In family F2, the previously described c.718C4T mutation in PAX6 was detected in the four affected members. This study adds new mutation to those previously reported in PAX6, providing further evidence for the genetic and phenotypic heterogeneity in individuals with aniridia ocular malformations.

BackgroundTo identify the genetic defect associated with autosomal recessive congenital cataract (ARCC), mental retardation (MR) and ARCC, MR and microcephaly present in most patients in four Tunisian consanguineous families.MethodsWe screened four genes implicated in congenital cataract by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly. Among its three genes PAX6, PITX3 and HSF4 are expressed in human brain and one gene LIM2 encodes for the protein MP20 that interact with the protein galectin-3 expressed in human brain and plays a crucial role in its development. All genes were screened by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly.ResultsWe report no mutation in the four genes of congenital cataract and its flanking regions. Only variations that did not segregate with the studied phenotypes (ARCC associated to MR, ARCC associated with MR and microcephaly) are reported. We detected three intronic variations in PAX6 gene: IVS4 -274insG (intron 4), IVS12 -174G>A (intron12) in the four studied families and IVS4 -195G>A (intron 4) in two families. Two substitutions polymorphisms in PITX3 gene: c.439 C>T (exon 3) and c.930 C>A (exon4) in one family. One intronic variation in HSF4 gene: IVS7 +93C>T (intron 7) identified in one family. And three intronic substitutions in LIM2 gene identified in all four studied families: IVS2 -24A>G (intron 2), IVS4 +32C>T (intron 4) and c.*15A>C (3'-downstream sequence).ConclusionAlthough the role of the four studied genes: PAX6, PITX3, HSF4 and LIM2 in both ocular and central nervous system development, we report the absence of mutations in all studied genes in four families with phenotypes associating cataract, MR and microcephaly.