The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat

UM Smith; M Consugar; Louise Tee; BM Mckee; Esther Maina; S Whelan; Neil Morgan; E Goranson; Paul Gissen; S Lilliquist; Irene Aligianis; CJ Ward; Shanaz Pasha; R Punyashhthiti; S Malik Sharif; PA Batman; CP Bennett; CG Woods; Carole McKeown; M Bucourt; CA Miller; Phillip Cox; L Algazali; RC Trembath; VE Torres; T Attie-Bitach; Deirdre Kelly; Eamonn Maher; VH Gattone; PC Harris; Colin Johnson

doi:10.1038/ng1713

The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat

UM Smith, M Consugar, Louise Tee, BM Mckee, Esther Maina, S Whelan, Neil Morgan, E Goranson, Paul Gissen, S Lilliquist, Irene Aligianis, CJ Ward, Shanaz Pasha, R Punyashhthiti, S Malik Sharif, PA Batman, CP Bennett, CG Woods, Carole McKeown, M BucourtCA Miller, Phillip Cox, L Algazali, RC Trembath, VE Torres, T Attie-Bitach, Deirdre Kelly, Eamonn Maher, VH Gattone, PC Harris, Colin Johnson

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Abstract

Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system (most commonly occipital encephalocele), hepatic ductal dysplasia and cysts and polydactyly. MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 (ref. 5) and MKS3 (ref. 6). We have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic to the Wpk locus in rat, which is a model with polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic mutations for five MKS3-linked consanguineous families. MKS3 is a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. It encodes a 995-amino acid seven-transmembrane receptor protein of unknown function that we have called meckelin.

Original language	English
Pages (from-to)	191-196
Number of pages	6
Journal	Nature Genetics
Volume	38
Issue number	2
DOIs	https://doi.org/10.1038/ng1713
Publication status	Published - 1 Feb 2006

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Smith, UM., Consugar, M., Tee, L., Mckee, BM., Maina, E., Whelan, S., Morgan, N., Goranson, E., Gissen, P., Lilliquist, S., Aligianis, I., Ward, CJ., Pasha, S., Punyashhthiti, R., Malik Sharif, S., Batman, PA., Bennett, CP., Woods, CG., McKeown, C., ... Johnson, C. (2006). The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. Nature Genetics, 38(2), 191-196. https://doi.org/10.1038/ng1713

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title = "The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat",

abstract = "Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system (most commonly occipital encephalocele), hepatic ductal dysplasia and cysts and polydactyly. MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 (ref. 5) and MKS3 (ref. 6). We have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic to the Wpk locus in rat, which is a model with polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic mutations for five MKS3-linked consanguineous families. MKS3 is a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. It encodes a 995-amino acid seven-transmembrane receptor protein of unknown function that we have called meckelin.",

author = "UM Smith and M Consugar and Louise Tee and BM Mckee and Esther Maina and S Whelan and Neil Morgan and E Goranson and Paul Gissen and S Lilliquist and Irene Aligianis and CJ Ward and Shanaz Pasha and R Punyashhthiti and {Malik Sharif}, S and PA Batman and CP Bennett and CG Woods and Carole McKeown and M Bucourt and CA Miller and Phillip Cox and L Algazali and RC Trembath and VE Torres and T Attie-Bitach and Deirdre Kelly and Eamonn Maher and VH Gattone and PC Harris and Colin Johnson",

year = "2006",

month = feb,

day = "1",

doi = "10.1038/ng1713",

language = "English",

volume = "38",

pages = "191--196",

journal = "Nature Genetics",

issn = "1546-1718",

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Smith, UM, Consugar, M, Tee, L, Mckee, BM, Maina, E, Whelan, S, Morgan, N, Goranson, E, Gissen, P, Lilliquist, S, Aligianis, I, Ward, CJ, Pasha, S, Punyashhthiti, R, Malik Sharif, S, Batman, PA, Bennett, CP, Woods, CG, McKeown, C, Bucourt, M, Miller, CA, Cox, P, Algazali, L, Trembath, RC, Torres, VE, Attie-Bitach, T, Kelly, D, Maher, E, Gattone, VH, Harris, PC & Johnson, C 2006, 'The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat', Nature Genetics, vol. 38, no. 2, pp. 191-196. https://doi.org/10.1038/ng1713

TY - JOUR

T1 - The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat

AU - Smith, UM

AU - Consugar, M

AU - Tee, Louise

AU - Mckee, BM

AU - Maina, Esther

AU - Whelan, S

AU - Morgan, Neil

AU - Goranson, E

AU - Gissen, Paul

AU - Lilliquist, S

AU - Aligianis, Irene

AU - Ward, CJ

AU - Pasha, Shanaz

AU - Punyashhthiti, R

AU - Malik Sharif, S

AU - Batman, PA

AU - Bennett, CP

AU - Woods, CG

AU - McKeown, Carole

AU - Bucourt, M

AU - Miller, CA

AU - Cox, Phillip

AU - Algazali, L

AU - Trembath, RC

AU - Torres, VE

AU - Attie-Bitach, T

AU - Kelly, Deirdre

AU - Maher, Eamonn

AU - Gattone, VH

AU - Harris, PC

AU - Johnson, Colin

PY - 2006/2/1

Y1 - 2006/2/1

N2 - Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system (most commonly occipital encephalocele), hepatic ductal dysplasia and cysts and polydactyly. MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 (ref. 5) and MKS3 (ref. 6). We have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic to the Wpk locus in rat, which is a model with polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic mutations for five MKS3-linked consanguineous families. MKS3 is a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. It encodes a 995-amino acid seven-transmembrane receptor protein of unknown function that we have called meckelin.

AB - Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system (most commonly occipital encephalocele), hepatic ductal dysplasia and cysts and polydactyly. MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 (ref. 5) and MKS3 (ref. 6). We have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic to the Wpk locus in rat, which is a model with polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic mutations for five MKS3-linked consanguineous families. MKS3 is a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. It encodes a 995-amino acid seven-transmembrane receptor protein of unknown function that we have called meckelin.

U2 - 10.1038/ng1713

DO - 10.1038/ng1713

M3 - Article

C2 - 16415887

SN - 1546-1718

VL - 38

SP - 191

EP - 196

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat

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