Özet:
In the framework of this study, genome wide linkage scans of the following five inherited disorders were evaluated with parametric programs and suggestive loci were subsequently investigated with fine-mapping studies and candidate gene approach. Split-Hand/Foot Malformation (SHFM) affects the central rays of the autopod. We identified a novel SHFM locus at 12q13.11-q13 and a homozygous WNT10b mutation (p.R332W) in all affected individuals plus in an asymptomatic female. We propose that either a second locus contributes to the manifestation of SHFM phenotype or a suppressor locus prevented trait manifestation in the non-penetrant female. This is the first reported WNT10b mutation on the pathogenesis of limb development and recessive mutation in SHFM. Hypomyelination and congenital cataract is a recessive white matter disorder caused by mutations in gene DRCTNNB1A. Here we report a large intragenic deletion that does not lead to congenital cataract in all of the patients in an afflicted family. A novel form of recessive cone rod dystrophy was mapped to chromosome 17p13.2-p13.1, and the disease gene was identified as GUCY2D encoding the retinal guanylyl cyclase gene. The mutation (p.I949T) resided in the catalytic domain of the protein where other mutations had previously been associated with Leber congenital amaurosis, a common cause of childhood blindness. The milder phenotype observed in our patients implicate that either the mutation does not disturb the catalytic activity completely or modifier locus/loci interfere with the phenotype. Lastly, a recessive form of mental retardation and a dominant arthrogryposis syndrome were mapped to chromosomes 7q21.3-q31.1 and 13q31.3-q32.1, respectively.
