Novel GUCY2D mutation causes phenotypic variability of Leber congenital amaurosis in a large kindred.

Background: Leber congenital amaurosis (LCA) is a severe retinal degenerative disease that manifests as blindness or poor vision in infancy. The purpose of this study was to clinically characterize and identify the cause of disease in a large inbred Bedouin Israeli tribe with LCA.

Methods: Thirty individuals of a single kindred, including eight affected with LCA, were recruited for this study.

Kohlschutter-Tonz syndrome: clinical and genetic insights gained from 16 cases deriving from a close-knit village in Northern Israel.

Background: Kohlschutter-Tonz syndrome (KTS; MIM 22675) is a rare autosomal recessive disorder characterized by intellectual impairment, spasticity, epilepsy, and amelogenesis imperfecta. We have recently identified the causative gene and mutation underlying KTS, namely, p.R157X, corresponding to ROGDI c.

The desmosterolosis phenotype: spasticity, microcephaly and micrognathia with agenesis of corpus callosum and loss of white matter.

Desmosterolosis is a rare autosomal recessive disorder of elevated levels of the cholesterol precursor desmosterol in plasma, tissue and cultured cells. With only two sporadic cases described to date with two very different phenotypes, the clinical entity arising from mutations in 24-dehydrocholesterol reductase (DHCR24) has yet to be defined. We now describe consanguineous Bedouin kindred with four surviving affected individuals, all presenting with severe failure to thrive, psychomotor retardation, microcephaly, micrognathia and spasticity with variable degree of hand contractures.