A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution

Edgar Otto, Julia Hoefele, Rainer Ruf, Adelheid M. Mueller, Karl S. Hiller, Matthias T.F. Wolf, Maria J. Schuermann, Achim Becker, Ralf Birkenhäger, Ralf Sudbrak, Hans C. Hennies, Peter Nürnberg, Friedhelm Hildebrandt

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

Nephronophthisis (NPHP) comprises a group of autosomal recessive cystic kidney diseases, which constitute the most frequent genetic cause for end-stage renal failure in children and young adults. The most prominent histologic feature of NPHP consists of development of renal fibrosis, which, in chronic renal failure of any origin, represents the pathogenic event correlated most strongly to loss of renal function. Four gene loci for NPHP have been mapped to chromosomes 2q13 (NPHP1), 9q22 (NPHP2), 3q22 (NPHP3), and 1p36 (NPHP4). At all four loci, linkage has also been demonstrated in families with the association of NPHP and retinitis pigmentosa, known as "Senior-Løken syndrome" (SLS). Identification of the gene for NPHP type 1 had revealed nephrocystin as a novel docking protein, providing new insights into mechanisms of cell-cell and cell-matrix signaling. We here report identification of the gene (NPHP4) causing NPHP type 4, by use of high-resolution haplotype analysis and by demonstration of nine likely loss-of-function mutations in six affected families. NPHP4 encodes a novel protein, nephroretinin, that is conserved in evolution-for example, in the nematode Caenorhabditis elegans. In addition, we demonstrate two loss-of-function mutations of NPHP4 in patients from two families with SLS. Thus, we have identified a novel gene with critical roles in renal tissue architecture and ophthalmic function.

LanguageEnglish
Pages1161-1167
Number of pages7
JournalAmerican Journal of Human Genetics
Volume71
Issue number5
DOIs
Publication statusPublished - 1 Jan 2002
Externally publishedYes

Fingerprint

Retinitis Pigmentosa
Kidney
Genes
Chronic Kidney Failure
Proteins
Cystic Kidney Diseases
Mutation
Caenorhabditis elegans
Haplotypes
Young Adult
Fibrosis
Chromosomes
Senior Loken Syndrome

Cite this

Otto, E., Hoefele, J., Ruf, R., Mueller, A. M., Hiller, K. S., Wolf, M. T. F., ... Hildebrandt, F. (2002). A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution. American Journal of Human Genetics, 71(5), 1161-1167. https://doi.org/10.1086/344395
Otto, Edgar ; Hoefele, Julia ; Ruf, Rainer ; Mueller, Adelheid M. ; Hiller, Karl S. ; Wolf, Matthias T.F. ; Schuermann, Maria J. ; Becker, Achim ; Birkenhäger, Ralf ; Sudbrak, Ralf ; Hennies, Hans C. ; Nürnberg, Peter ; Hildebrandt, Friedhelm. / A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution. In: American Journal of Human Genetics. 2002 ; Vol. 71, No. 5. pp. 1161-1167.
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abstract = "Nephronophthisis (NPHP) comprises a group of autosomal recessive cystic kidney diseases, which constitute the most frequent genetic cause for end-stage renal failure in children and young adults. The most prominent histologic feature of NPHP consists of development of renal fibrosis, which, in chronic renal failure of any origin, represents the pathogenic event correlated most strongly to loss of renal function. Four gene loci for NPHP have been mapped to chromosomes 2q13 (NPHP1), 9q22 (NPHP2), 3q22 (NPHP3), and 1p36 (NPHP4). At all four loci, linkage has also been demonstrated in families with the association of NPHP and retinitis pigmentosa, known as {"}Senior-L{\o}ken syndrome{"} (SLS). Identification of the gene for NPHP type 1 had revealed nephrocystin as a novel docking protein, providing new insights into mechanisms of cell-cell and cell-matrix signaling. We here report identification of the gene (NPHP4) causing NPHP type 4, by use of high-resolution haplotype analysis and by demonstration of nine likely loss-of-function mutations in six affected families. NPHP4 encodes a novel protein, nephroretinin, that is conserved in evolution-for example, in the nematode Caenorhabditis elegans. In addition, we demonstrate two loss-of-function mutations of NPHP4 in patients from two families with SLS. Thus, we have identified a novel gene with critical roles in renal tissue architecture and ophthalmic function.",
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Otto, E, Hoefele, J, Ruf, R, Mueller, AM, Hiller, KS, Wolf, MTF, Schuermann, MJ, Becker, A, Birkenhäger, R, Sudbrak, R, Hennies, HC, Nürnberg, P & Hildebrandt, F 2002, 'A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution', American Journal of Human Genetics, vol. 71, no. 5, pp. 1161-1167. https://doi.org/10.1086/344395

A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution. / Otto, Edgar; Hoefele, Julia; Ruf, Rainer; Mueller, Adelheid M.; Hiller, Karl S.; Wolf, Matthias T.F.; Schuermann, Maria J.; Becker, Achim; Birkenhäger, Ralf; Sudbrak, Ralf; Hennies, Hans C.; Nürnberg, Peter; Hildebrandt, Friedhelm.

In: American Journal of Human Genetics, Vol. 71, No. 5, 01.01.2002, p. 1161-1167.

Research output: Contribution to journalArticle

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T1 - A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution

AU - Otto, Edgar

AU - Hoefele, Julia

AU - Ruf, Rainer

AU - Mueller, Adelheid M.

AU - Hiller, Karl S.

AU - Wolf, Matthias T.F.

AU - Schuermann, Maria J.

AU - Becker, Achim

AU - Birkenhäger, Ralf

AU - Sudbrak, Ralf

AU - Hennies, Hans C.

AU - Nürnberg, Peter

AU - Hildebrandt, Friedhelm

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