OCRL1 mutation analysis in French Lowe syndrome patients: Implications formolecular diagnosis strategy and genetic counseling

The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked recessivel y inherited disease characterized by a severe pleiotropic phenotype includi ng mental retardation, bilateral congenital cataract, and renal Fanconi syn drome. The gene responsible for OCRL encodes an inositol polyphosphate-5-ph osphatase. We performed mutation analysis in 36 families and characterized 27 new mutations with two of them being recurrent mutations. The panel of m utations consisted of 27 truncating mutations (frameshift, nonsense, splice site mutations, and large genomic deletions), one in frame deletion, and s ix missense mutations. The four large genomic deletions occurred in the fir st half of the gene, whereas all the remaining mutations took place in the second part of the gene and were concentrated in a few exons. This distribu tion may be of interest in terms of screening strategy when looking for unk nown mutations, Haplotyping of the families was performed to analyze segreg ation of the mutated loci, and revealed a somatic mosaicism in one family T his is the second case of mosaicism we characterized in a total panel of 44 unrelated families affected by Lowe's syndrome. Considering the low number of families investigated, it appeared that somatic and germinal mosaicisms are quite common in this disease and must be taken into account for geneti c counseling. Hum Mutat 16:157-165, 2000. (C) 2000 Wiley Liss, Inc.