Human Molecular Genetics, Vol 6, 2317-2323, Copyright © 1997 by Oxford University Press
S Saunier, J Calado, R Heilig, F Silbermann, F Benessy, G Morin, M Konrad, M Broyer, MC Gubler, J Weissenbach and C Antignac
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 approximately 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.
ARTICLES
A novel gene that encodes a protein with a putative src homology 3 domain is a candidate gene for familial juvenile nephronophthisis
INSERM U 423, Tour Lavoisier, 6 degrees etage, Hopital Necker-Enfants Malades, 75743 Paris Cedex 15, France.
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