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Title
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A novel gene that encodes a protein with a putative src homology 3 domain is a candidate gene for familial juvenile nephronophthisis.
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Authors
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S.Saunier,
J.Calado,
R.Heilig,
F.Silbermann,
F.Benessy,
G.Morin,
M.Konrad,
M.Broyer,
M.C.Gubler,
J.Weissenbach,
C.Antignac.
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Ref.
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Hum Mol Genet, 1997,
6,
2317-2323.
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PubMed id
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Abstract
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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.
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