RESUMO
Homozygous deletion of NPHP1 can lead to isolated nephronophthisis (NPHP) and syndromic disorders. However, the phenotype of scalp tumor and hydroureteronephrosis in NPHP patients with homozygous deletion of NPHP1 has not been reported. Clinical data, laboratory results, and genetic testing of 4 NPHP patients were collected. Examination of their eyes, heart, and urinary tract and of their hepatobiliary, skeletal, and central nervous systems was evaluated. Isolated NPHP was observed in 1 case, and syndromic disorders were observed in the other 3 patients. Their syndromic disorders showed NPHP combined with central nervous system defects, eye involvement, scalp tumor, arachnoid cyst, or hydroureteronephrosis. Large homozygous deletions covering the whole NPHP1 gene locus were identified in all 4 patients. We report a novel phenotype of scalp tumor and hydroureteronephrosis in NPHP patients with homozygous deletion of NPHP1, paving an avenue for further research on NPHP1-associated deformity in the skin and the urinary system.
Assuntos
Doenças Renais Císticas , Falência Renal Crônica , Neoplasias , Humanos , Homozigoto , Falência Renal Crônica/genética , Proteínas de Membrana/genética , Proteínas do Citoesqueleto/genética , Couro Cabeludo/patologia , Deleção de Sequência , Proteínas Adaptadoras de Transdução de Sinal/genética , Doenças Renais Císticas/genética , Doenças Renais Císticas/patologiaRESUMO
BACKGROUND: Nephronophthisis (NPHP) is the most common genetic cause of end-stage renal disease (ESRD) in children. This study was performed to explore the pathogenic gene mutations and clinical and pathological features of Chinese patients with NPHP. METHODS: Patients for whom causative mutations were not identified in our previous study, as well as those recruited later, were subjected to whole-exome next-generation sequencing (NGS) or the exome of 63 primary cilia disease genes. RESULTS: We recruited 55 patients (27 boys and 28 girls) from 48 families, mainly from South China. We subjected 35 patients to NGS. Disease-causing mutations were revealed in seven more families (nine patients) by NGS. In total, disease-causing mutations were identified in 25 patients from 19 families, accounting for 39.6% (19/48) of all families, and novel mutation rate was 77.8% (35/45). NPHP1 and NPHP3 mutations were identified in 14.6% (7/48) and 12.5% (6/48) of all families, respectively. The patient with CEP83 mutations presented with prominent glomerular cysts and glomeruli dysplasia without extrarenal involvement. CONCLUSION: A high novel mutation rate was identified, and disease-causing mutations of NPHP3 prevailed in this group of Chinese NPHP patients. This is the second report of a patient with CEP83 mutations.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas do Citoesqueleto/genética , Sequenciamento de Nucleotídeos em Larga Escala , Doenças Renais Císticas/congênito , Cinesinas/genética , Povo Asiático , Criança , Pré-Escolar , Biologia Computacional , Feminino , Humanos , Lactente , Recém-Nascido , Doenças Renais Císticas/genética , Masculino , MutaçãoRESUMO
AIM: The present study was designed to explore mutations of NPHP2 and NPHP3 and clinical features in 18 Chinese infantile nephronophthisis (NPHP) patients. METHODS: Patients were subjected to screen for mutations in both NPHP2 and NPHP3, and clinical data were collected. RESULTS: Eighteen patients from 17 families were included in this study. Eight of 17 (47.1%) patients detected were identified to have mutations in NPHP3, but none had a mutation in NPHP2. Of the patients with NPHP3 mutations, four had compound heterozygous mutations, and the other four harboured single heterozygous mutations. Ten of the NPHP3 mutations were novel. Low molecular weight proteinuria was observed in all 16 detected patients. Renal histology were available in seven children, five patients showed infantile type NPHP features, and the other two patients from the same family showed juvenile type NPHP features. Liver involvement was observed in all patients with NPHP3 mutations and congenital heart disease in two patients harbouring NPHP3 mutation of c.2369 T > C (p.L790P). CONCLUSIONS: In this group of infantile NPHP patients, mutations of NPHP3 were prevalent, whereas mutation of NPHP2 was absent. Genotype to phenotype correlations were observed in patients with NPHP3 mutations and all patients with NPHP3 mutations showed renal-hepatic phenotype.
Assuntos
Doenças Renais Císticas/genética , Cinesinas/genética , Mutação , Sequência de Aminoácidos , Povo Asiático/genética , Pré-Escolar , China , Análise Mutacional de DNA , Feminino , Frequência do Gene , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/etnologia , Cardiopatias Congênitas/genética , Heterozigoto , Humanos , Lactente , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/etnologia , Hepatopatias/diagnóstico , Hepatopatias/etnologia , Hepatopatias/genética , Masculino , Dados de Sequência Molecular , Linhagem , Fenótipo , Proteinúria/diagnóstico , Proteinúria/etnologia , Proteinúria/genética , Fatores de Risco , Fatores de Transcrição/genéticaRESUMO
Senior-Løken syndrome is a rare syndromic form of nephronophthisis that is associated with retinal dystrophy. Presently, seven genes (NPHP1-6 and NPHP10) have been associated with Senior-Løken syndrome. NPHP5 mutations are known to cause classical Senior-Løken syndrome. Here, we report two sisters (II-4, II-5) from a Chinese Han ethnic family who presented with classical Senior-Løken syndrome. Both affected sisters exhibited Leber's congenital amaurosis and juvenile nephronophthisis that progressed to end-stage renal disease by the age of 16 years and 9 months in patient II-4 and 12 years and 9 months in patient II-5. Sequence analysis showed a homozygous truncated mutation in NPHP5, c.1090C>T (p.R364X), in the patient II-4. This mutation is predicted to introduce a new open reading frame that results in the truncation of the C-terminal 235 amino acids of nephrocystin-5 and its consequent loss of function. Both parents carried a single heterozygous mutation in the same position, and no homozygous deletion of NPHP1 was found in this pedigree.