Absence of mutations in four genes encoding for congenital cataract and expressed in the human brain in Tunisian families with cataract and mental retardation

Faouzi Mâazoul,Abdelhafid Kraiem,Hedi Bouzid,Manèl Chograni,Habiba B Bouhamed Chaabouni,Myriam Chaabouni

doi:10.1186/1471-2415-11-35

Abstract

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.

Highlights

To 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
We analysed the four genes: LIM2, PAX6, PITX3 and HSF4 in four consanguineous unrelated Tunisian families with ARCC associated with mental retardation (MR) for two patients belonging to the same family and ARCC associated to MR and microcephaly for the others from the four studied families
All four families were of Tunisian origin and were enrolled in a genetic research program in the laboratory of Human Genetics, in the faculty of medicine (Tunis, Tunisia) because of two affected brothers belonging to family F2 with ARCC and MR and seven affected patients from the four studied families (F1, F2, F3, F4) with ARCC, MR and microcephaly

Summary

Introduction

To 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. Among genes encoding for membrane proteins (MIP), LIM2 gene (lens intrinsic membrane protein-2) involved in autosomal recessive congenital cataract [7,8]. It encodes an abundant integral lens membrane protein MP20 which is a new regulatory protein important for mammalian lens fiber cell junctional formation [9]. Lens-specific MP20 is classified as a member of the PMP22/EMP/MP20 subfamily of tetraspanins [10] and adds to a growing list of ligands of galectin-3[11], a known adhesion modulator that is expressed by microglial cells of adult brain [12] and contributes to injury in the deep gray matter areas of the brain [13]

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