[Show abstract][Hide abstract] ABSTRACT: Cystinuria is an autosomal recessive disease that is manifested by the development of kidney stones. Mutations in SLC3A1 cause type I disease, while mutations in SLC7A9 are associated with non-type I disease. In Israel, cystinuria is especially common among Libyan Jews who suffer from non-type I disease.
To compare clinical manifestations of patients with mutations in SLC3A1 to those with mutations in SLC7A9, and to assess the carrier rate among unaffected Libyan Jewish controls.
Clinical manifestations were evaluated in patients with mutations in SLC3A1 and in patients with mutations in SLC7A9. Carrier rates for two SLC7A9 mutations were assessed in 287 unaffected Libyan Jewish controls.
Twelve patients with mutations in SLC3A1 were compared to 15 patients with mutations in SLC7A9. No differences were detected between the patients with mutations in SLC3A1 and those with mutations in SLC7A9 in relation to the age of disease onset, the estimated number of stones, the number of invasive procedures, the number of patients receiving drug therapy, or the patients' urinary pH. Eleven of the unaffected Libyan Jewish controls were found to be heterozygotes for the V170M mutation, establishing a carrier rate of 1:25. The 1584 + 3 del AAGT mutation was not found in any of the Libyan Jewish controls.
Mutations in SLC3A1 and SLC7A9 cystinuria patients result in indistinguishable disease manifestations. The high carrier rate among Libyan Jews is a result of a single missense mutation, V170M.
Preview · Article · Jul 2003 · The Israel Medical Association journal: IMAJ
[Show abstract][Hide abstract] ABSTRACT: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive inherited neurological disorder characterized by macrocephaly, deterioration in motor functions and cerebellar ataxia. In Israel the disease is found in an increased frequency among Libyan Jews. The disease is caused by mutations in the MLC1 gene, which encodes a putative CNS membrane transporter. We describe three novel mutations (p.G59E, p.P92S, and 134_136insC) in seven MLC families. One of these mutations, p.G59E, was found in the vast majority of MLC patients in Israel. Screening of 200 normal Libyan Jewish individuals for the p.G59E mutation, revealed a carrier rate of 1/40 compared with an expected carrier rate of 1/81. Several explanations could account for this difference the most likely one is an admixture of the Libyan Jewish population.