RESUMO
Nephronophthisis is an autosomal recessive cystic kidney disease characterized by tubular interstitial infiltration, periglomerular fibrosis, and cysts, and is the most frequent genetic cause of end-stage renal disease in children. Nephronophthisis is pleiotropic as almost all the causative genes are involved in primary cilium and centrosome function which are found in almost all human cells. Genetic heterogeneity in nephronophthisis makes the molecular and genetic diagnosis somewhat difficult. Homozygous deletions in the nephronophthisis 1 (NPHP1) gene are the major contributor of nephronophthisis cases, while other genes accounts for less than 3% each. Nephronophthisis-related ciliopathy is a term used for extrarenal symptoms in addition to nephronophthisis. Herein, we are reporting the molecular study of 7 children from independent families fulfilling the criteria of nephronophthisis. A deletion analysis of the NPHP1 gene was performed in each case, and NPHP5 mutation screening was performed in the absence of such deletion in patients with Senior Loken syndrome.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Ligação a Calmodulina/genética , Ciliopatias/genética , Códon sem Sentido , Deleção de Genes , Doenças Renais Císticas/congênito , Amaurose Congênita de Leber/genética , Proteínas de Membrana/genética , Atrofias Ópticas Hereditárias/genética , Ciliopatias/complicações , Ciliopatias/diagnóstico , Proteínas do Citoesqueleto , Progressão da Doença , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , Doenças Renais Císticas/complicações , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/genética , Amaurose Congênita de Leber/complicações , Amaurose Congênita de Leber/diagnóstico , Masculino , Atrofias Ópticas Hereditárias/complicações , Atrofias Ópticas Hereditárias/diagnóstico , Paquistão , Linhagem , FenótipoRESUMO
UNLABELLED: Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and mucosal lesions and hoarseness appearing in early childhood that is caused by homozygous or compound heterozygous mutations in the ECM1 gene located on chromosome 1q21. The aim of the study was to investigate the molecular genetic defect underlying lipoid proteinosis in a consanguineous Pakistani family. METHODS: Genotyping of seven members of the family was performed by amplifying microsatellite markers, tightly linked to the ECM1 gene. To screen for mutations in the ECM1 gene, all of its exons and splice junctions were PCR amplified from genomic DNA and analyzed by SSCP and sequenced directly in an ABI 3130 genetic analyzer. RESULTS: The results revealed linkage of the LP family to the ECM1 locus. Sequence analysis of the coding exons and splice junctions of the ECM1 gene revealed a novel homozygous mutation (c.616C > T) in exon 6, predicted to replace glutamine with stop codon (p.Q206X) at amino acid position 206. CONCLUSIONS: The finding of a novel mutation in Pakistani family extends the body of evidence that supports the importance of ECM1 gene for the development of lipoid proteinosis.
