Mutations in the VLGR1 Gene Implicate G-Protein Signaling in the Pathogenesis of Usher Syndrome Type II

Michael Weston, Mirjam W J Luijendijk, Kurt D. Humphrey, Claes Möller, William J. Kimberling

Research output: Contribution to journalArticle

199 Citations (Scopus)

Abstract

Usher syndrome type II (USH2) is a genetically heterogeneous autosomal recessive disorder with at least three genetic subtypes (USH2A, USH2B, and USH2C) and is classified phenotypically as congenital hearing loss and progressive retinitis pigmentosa. The VLGR1 (MASS1) gene in the 5q14.3-q21.1 USH2C locus was considered a likely candidate on the basis of its protein motif structure and expressed-sequence-tag representation from both cochlear and retinal subtracted libraries. Denaturing high-performance liquid chromatography and direct sequencing of polymerase-chain-reaction products amplified from 10 genetically independent patients with USH2C and 156 other patients with USH2 identified four isoform-specific VLGR1 mutations (Q2301X, I2906FS, M2931FS, and T6244X) from three families with USH2C, as well as two sporadic cases. All patients with VLGR1 mutations are female, a significant deviation from random expectations. The ligand(s) for the VLGR1 protein is unknown, but on the basis of its potential extracellular and intracellular protein-protein interaction domains and its wide mRNA expression profile, it is probable that VLGR1 serves diverse cellular and signaling processes. VLGR1 mutations have been previously identified in both humans and mice and are associated with a reflex-seizure phenotype in both species. The identification of additional VLGR1 mutations to test whether a phenotype/genotype correlation exists, akin to that shown for other Usher syndrome disease genes, is warranted.

Original languageEnglish
Pages (from-to)357-366
Number of pages10
JournalAmerican Journal of Human Genetics
Volume74
Issue number2
DOIs
StatePublished - Feb 2004

Fingerprint

Usher Syndromes
GTP-Binding Proteins
Mutation
Genes
Protein Interaction Domains and Motifs
Amino Acid Motifs
Retinitis Pigmentosa
Cochlea
Expressed Sequence Tags
Genetic Association Studies
Hearing Loss
Reflex
Protein Isoforms
Seizures
High Pressure Liquid Chromatography
Ligands
Phenotype
Polymerase Chain Reaction
Messenger RNA
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Mutations in the VLGR1 Gene Implicate G-Protein Signaling in the Pathogenesis of Usher Syndrome Type II. / Weston, Michael; Luijendijk, Mirjam W J; Humphrey, Kurt D.; Möller, Claes; Kimberling, William J.

In: American Journal of Human Genetics, Vol. 74, No. 2, 02.2004, p. 357-366.

Research output: Contribution to journalArticle

Weston, Michael ; Luijendijk, Mirjam W J ; Humphrey, Kurt D. ; Möller, Claes ; Kimberling, William J. / Mutations in the VLGR1 Gene Implicate G-Protein Signaling in the Pathogenesis of Usher Syndrome Type II. In: American Journal of Human Genetics. 2004 ; Vol. 74, No. 2. pp. 357-366.
@article{9b549f1867fc4649b61823ba2c5f8afe,
title = "Mutations in the VLGR1 Gene Implicate G-Protein Signaling in the Pathogenesis of Usher Syndrome Type II",
abstract = "Usher syndrome type II (USH2) is a genetically heterogeneous autosomal recessive disorder with at least three genetic subtypes (USH2A, USH2B, and USH2C) and is classified phenotypically as congenital hearing loss and progressive retinitis pigmentosa. The VLGR1 (MASS1) gene in the 5q14.3-q21.1 USH2C locus was considered a likely candidate on the basis of its protein motif structure and expressed-sequence-tag representation from both cochlear and retinal subtracted libraries. Denaturing high-performance liquid chromatography and direct sequencing of polymerase-chain-reaction products amplified from 10 genetically independent patients with USH2C and 156 other patients with USH2 identified four isoform-specific VLGR1 mutations (Q2301X, I2906FS, M2931FS, and T6244X) from three families with USH2C, as well as two sporadic cases. All patients with VLGR1 mutations are female, a significant deviation from random expectations. The ligand(s) for the VLGR1 protein is unknown, but on the basis of its potential extracellular and intracellular protein-protein interaction domains and its wide mRNA expression profile, it is probable that VLGR1 serves diverse cellular and signaling processes. VLGR1 mutations have been previously identified in both humans and mice and are associated with a reflex-seizure phenotype in both species. The identification of additional VLGR1 mutations to test whether a phenotype/genotype correlation exists, akin to that shown for other Usher syndrome disease genes, is warranted.",
author = "Michael Weston and Luijendijk, {Mirjam W J} and Humphrey, {Kurt D.} and Claes M{\"o}ller and Kimberling, {William J.}",
year = "2004",
month = "2",
doi = "10.1086/381685",
language = "English",
volume = "74",
pages = "357--366",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Mutations in the VLGR1 Gene Implicate G-Protein Signaling in the Pathogenesis of Usher Syndrome Type II

AU - Weston, Michael

AU - Luijendijk, Mirjam W J

AU - Humphrey, Kurt D.

AU - Möller, Claes

AU - Kimberling, William J.

PY - 2004/2

Y1 - 2004/2

N2 - Usher syndrome type II (USH2) is a genetically heterogeneous autosomal recessive disorder with at least three genetic subtypes (USH2A, USH2B, and USH2C) and is classified phenotypically as congenital hearing loss and progressive retinitis pigmentosa. The VLGR1 (MASS1) gene in the 5q14.3-q21.1 USH2C locus was considered a likely candidate on the basis of its protein motif structure and expressed-sequence-tag representation from both cochlear and retinal subtracted libraries. Denaturing high-performance liquid chromatography and direct sequencing of polymerase-chain-reaction products amplified from 10 genetically independent patients with USH2C and 156 other patients with USH2 identified four isoform-specific VLGR1 mutations (Q2301X, I2906FS, M2931FS, and T6244X) from three families with USH2C, as well as two sporadic cases. All patients with VLGR1 mutations are female, a significant deviation from random expectations. The ligand(s) for the VLGR1 protein is unknown, but on the basis of its potential extracellular and intracellular protein-protein interaction domains and its wide mRNA expression profile, it is probable that VLGR1 serves diverse cellular and signaling processes. VLGR1 mutations have been previously identified in both humans and mice and are associated with a reflex-seizure phenotype in both species. The identification of additional VLGR1 mutations to test whether a phenotype/genotype correlation exists, akin to that shown for other Usher syndrome disease genes, is warranted.

AB - Usher syndrome type II (USH2) is a genetically heterogeneous autosomal recessive disorder with at least three genetic subtypes (USH2A, USH2B, and USH2C) and is classified phenotypically as congenital hearing loss and progressive retinitis pigmentosa. The VLGR1 (MASS1) gene in the 5q14.3-q21.1 USH2C locus was considered a likely candidate on the basis of its protein motif structure and expressed-sequence-tag representation from both cochlear and retinal subtracted libraries. Denaturing high-performance liquid chromatography and direct sequencing of polymerase-chain-reaction products amplified from 10 genetically independent patients with USH2C and 156 other patients with USH2 identified four isoform-specific VLGR1 mutations (Q2301X, I2906FS, M2931FS, and T6244X) from three families with USH2C, as well as two sporadic cases. All patients with VLGR1 mutations are female, a significant deviation from random expectations. The ligand(s) for the VLGR1 protein is unknown, but on the basis of its potential extracellular and intracellular protein-protein interaction domains and its wide mRNA expression profile, it is probable that VLGR1 serves diverse cellular and signaling processes. VLGR1 mutations have been previously identified in both humans and mice and are associated with a reflex-seizure phenotype in both species. The identification of additional VLGR1 mutations to test whether a phenotype/genotype correlation exists, akin to that shown for other Usher syndrome disease genes, is warranted.

UR - http://www.scopus.com/inward/record.url?scp=0842328857&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0842328857&partnerID=8YFLogxK

U2 - 10.1086/381685

DO - 10.1086/381685

M3 - Article

VL - 74

SP - 357

EP - 366

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 2

ER -