A novel gene that encodes a protein with a putative src homology 3 domain is a candidate gene for familial juvenile nephronophthisis

被引:117
作者
Saunier, S
Calado, J
Heilig, R
Silbermann, F
Benessy, F
Morin, G
Konrad, M
Broyer, M
Gubler, MC
Weissenbach, J
Antignac, C
机构
[1] HOP NECKER ENFANTS MALAD,INSERM U 423,F-75743 PARIS 15,FRANCE
[2] CNRS,URA 1922,F-91000 EVRY,FRANCE
[3] UNIV PARIS 05,HOP NECKER ENFANTS MALAD,SERV NEPHROL PEDIAT,F-75743 PARIS 15,FRANCE
关键词
D O I
10.1093/hmg/6.13.2317
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Familial juvenile nephronophthisis (NPH) is an autosomal recessive, genetically heterogeneous disorder, representing the most frequent inherited cause of chronic renal failure in children, One of the responsible loci, NPH1, has been mapped to 2q13, The presence of large homozygous deletions of similar to 250 kb in the majority of affected patients allowed us to define a minimal deletion interval for NPH1, A BAC contig covering this interval was established, Combination of large scale genomic sequencing, cDNA selection and computer-aided analysis led to the characterization of two transcriptional units, One encodes the already known BENE protein, and the other encodes a novel protein of at least 732 amino acids containing a putative src homology 3 domain, In two patients carrying the large deletion of the NPH1 region on only one allele, two mutations were detected in two independent exons of the novel gene, One consists of a single base deletion, causing a frameshift, and the other is a G-->A substitution in the consensus 5' splice donor site, Both mutations thus potentially generate null mutants, One of these mutations was found to segregate with the disease in the family, and the second appeared to be a de novo mutation, We therefore conclude that this novel gene is a strong candidate for NPH.
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页码:2317 / 2323
页数:7
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