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Posterior microphthalmia (PM) is a relatively rare autosomal recessive condition with normal anterior segment and small posterior segment resulting in high hyperopia and retinal folding. It is an uncommon subtype of microphthalmia that has been mostly reported to coexist with several other ophthalmic conditions and to occur in sporadic cases. The membrane-type frizzled-related protein ( MFRP) is the only gene so far reported implicated in autosomal recessive, non-syndromic and syndromic forms of PM. Here, we performed a clinical and genetic analysis using six consanguineous families ascertained from different regions of Tunisia and affected with non-syndromic PM that segregates as an autosomal recessive trait. To identify the disease-causing defect in these families, we first analysed MFRP gene, then some candidate genes ( CHX10, OPA1, MITF, SOX2, CRYBB1-3 and CRYBA4) and loci (MCOP1, NNO1 and NNO2) previously implicated in different forms of microphthalmia. After exclusion of these genes and loci, we performed a genome-wide scan using a high density single nucleotide polymorphism (SNP) array 50 K in a large consanguineous pedigree. SNP genotyping revealed eight homozygous candidate regions on chromosomes 1, 2, 3, 6, 15, 17 and 21. Linkage analysis with additional microsatellite markers only retained the 2q37.1 region with a maximum LOD score of 8.85 obtained for D2S2344 at θ = 0.00. Further investigations are compatible for linkage of four more families to this region with a refined critical interval of 2.35 Mb. The screening of five candidate genes SAG, PDE6D, CHRND, CHRNG and IRK13 did not reveal any disease-causing mutation. [ABSTRACT FROM AUTHOR]

Microspherophakia seems to be the most specific feature of the Weill–Marchesani Syndrome, which could be due to mutations within the ADAMTS10 gene. As the locus responsible for isolated microspherophakia is still unknown, because the reported cases are rare, we checked whether the ADAMTS10 gene is involved in isolated microspherophakia in a Tunisian family. A consanguineous family (MSP-M), including six family members and two patients, presented with decreased vision secondary to bilateral isolated microspherophakia. A linkage analysis was carried out using microsatellite markers flanking the ADAMTS10 candidate gene. In the MSP-M family, isolated microspherophakia is likely inherited as an autosomal-recessive disease. Using a homozygosity-mapping strategy, haplotypic analysis using four STRs showed an exclusion of linkage between the ADAMTS10 gene and the disease locus in this family. Our study suggests that isolated microspherophakia and the Weill–Marchesani Syndrome are not allelic to the ADAMTS10 gene. [ABSTRACT FROM AUTHOR]