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

Ursula M. Smith, Mark Consugar, Louise J. Tee, Brandy M. McKee, Esther N. Maina, Shelly Whelan, Neil V. Morgan, Erin Goranson, Paul Gissen, Stacie Lilliquist, Irene A. Aligianis, Christopher J. Ward, Shanaz Pasha, Rachaneekorn Punyashthiti, Saghira Malik Sharif, Philip A. Batman, Christopher P. Bennett, C. Geoffrey Woods, Carole McKeown, Martine BucourtCaroline A. Miller, Phillip Cox, Lihadh AlGazali, Richard C. Trembath, Vicente Torres, Tania Attie-Bitach, Deirdre A. Kelly, Eamonn R. Maher, Vincent H. Gattone, Peter C Harris, Colin A. Johnson

Research output: Contribution to journalArticle

179 Citations (Scopus)

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 polydactyly1-3. 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 hydrocephalus7,8. 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 languageEnglish (US)
Pages (from-to)191-196
Number of pages6
JournalNature Genetics
Volume38
Issue number2
DOIs
StatePublished - Feb 2006

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Agenesis of Corpus Callosum
Genes
Encephalocele
Kidney
Polycystic Kidney Diseases
Proteins
Liver
Cysts
Organism Cloning
Central Nervous System
Amino Acids
Mutation
Brain
Meckel syndrome type 1

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Smith, U. M., Consugar, M., Tee, L. J., McKee, B. M., Maina, E. N., Whelan, S., ... Johnson, C. A. (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

The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. / Smith, Ursula M.; Consugar, Mark; Tee, Louise J.; McKee, Brandy M.; Maina, Esther N.; Whelan, Shelly; Morgan, Neil V.; Goranson, Erin; Gissen, Paul; Lilliquist, Stacie; Aligianis, Irene A.; Ward, Christopher J.; Pasha, Shanaz; Punyashthiti, Rachaneekorn; Sharif, Saghira Malik; Batman, Philip A.; Bennett, Christopher P.; Woods, C. Geoffrey; McKeown, Carole; Bucourt, Martine; Miller, Caroline A.; Cox, Phillip; AlGazali, Lihadh; Trembath, Richard C.; Torres, Vicente; Attie-Bitach, Tania; Kelly, Deirdre A.; Maher, Eamonn R.; Gattone, Vincent H.; Harris, Peter C; Johnson, Colin A.

In: Nature Genetics, Vol. 38, No. 2, 02.2006, p. 191-196.

Research output: Contribution to journalArticle

Smith, UM, Consugar, M, Tee, LJ, McKee, BM, Maina, EN, Whelan, S, Morgan, NV, Goranson, E, Gissen, P, Lilliquist, S, Aligianis, IA, Ward, CJ, Pasha, S, Punyashthiti, R, Sharif, SM, Batman, PA, Bennett, CP, Woods, CG, McKeown, C, Bucourt, M, Miller, CA, Cox, P, AlGazali, L, Trembath, RC, Torres, V, Attie-Bitach, T, Kelly, DA, Maher, ER, Gattone, VH, Harris, PC & Johnson, CA 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
Smith UM, Consugar M, Tee LJ, McKee BM, Maina EN, Whelan S et al. The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. Nature Genetics. 2006 Feb;38(2):191-196. https://doi.org/10.1038/ng1713
Smith, Ursula M. ; Consugar, Mark ; Tee, Louise J. ; McKee, Brandy M. ; Maina, Esther N. ; Whelan, Shelly ; Morgan, Neil V. ; Goranson, Erin ; Gissen, Paul ; Lilliquist, Stacie ; Aligianis, Irene A. ; Ward, Christopher J. ; Pasha, Shanaz ; Punyashthiti, Rachaneekorn ; Sharif, Saghira Malik ; Batman, Philip A. ; Bennett, Christopher P. ; Woods, C. Geoffrey ; McKeown, Carole ; Bucourt, Martine ; Miller, Caroline A. ; Cox, Phillip ; AlGazali, Lihadh ; Trembath, Richard C. ; Torres, Vicente ; Attie-Bitach, Tania ; Kelly, Deirdre A. ; Maher, Eamonn R. ; Gattone, Vincent H. ; Harris, Peter C ; Johnson, Colin A. / The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. In: Nature Genetics. 2006 ; Vol. 38, No. 2. pp. 191-196.
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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 polydactyly1-3. 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 hydrocephalus7,8. 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.",
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AU - Maina, Esther N.

AU - Whelan, Shelly

AU - Morgan, Neil V.

AU - Goranson, Erin

AU - Gissen, Paul

AU - Lilliquist, Stacie

AU - Aligianis, Irene A.

AU - Ward, Christopher J.

AU - Pasha, Shanaz

AU - Punyashthiti, Rachaneekorn

AU - Sharif, Saghira Malik

AU - Batman, Philip A.

AU - Bennett, Christopher P.

AU - Woods, C. Geoffrey

AU - McKeown, Carole

AU - Bucourt, Martine

AU - Miller, Caroline A.

AU - Cox, Phillip

AU - AlGazali, Lihadh

AU - Trembath, Richard C.

AU - Torres, Vicente

AU - Attie-Bitach, Tania

AU - Kelly, Deirdre A.

AU - Maher, Eamonn R.

AU - Gattone, Vincent H.

AU - Harris, Peter C

AU - Johnson, Colin A.

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