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.
authors.affiliation: Section of Medical and Molecular Genetics, Division of Reproductive and Child Health, University of Birmingham Medical School, Birmingham B15 2TT, UK.
authors.forename: Ursula M
authors.initials: UM
authors.lastname: Smith
authors.forename: Mark
authors.initials: M
authors.lastname: Consugar
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Tee
authors.forename: Brandy M
authors.initials: BM
authors.lastname: McKee
authors.forename: Esther N
authors.initials: EN
authors.lastname: Maina
authors.forename: Shelly
authors.initials: S
authors.lastname: Whelan
authors.forename: Neil V
authors.initials: NV
authors.lastname: Morgan
authors.forename: Erin
authors.initials: E
authors.lastname: Goranson
authors.forename: Paul
authors.initials: P
authors.lastname: Gissen
authors.forename: Stacie
authors.initials: S
authors.lastname: Lilliquist
authors.forename: Irene A
authors.initials: IA
authors.lastname: Aligianis
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ward
authors.forename: Shanaz
authors.initials: S
authors.lastname: Pasha
authors.forename: Rachaneekorn
authors.initials: R
authors.lastname: Punyashthiti
authors.forename: Saghira
authors.initials: S
authors.lastname: Malik Sharif
authors.forename: Philip A
authors.initials: PA
authors.lastname: Batman
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Bennett
authors.forename: C Geoffrey
authors.initials: CG
authors.lastname: Woods
authors.forename: Carole
authors.initials: C
authors.lastname: McKeown
authors.forename: Martine
authors.initials: M
authors.lastname: Bucourt
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Miller
authors.forename: Phillip
authors.initials: P
authors.lastname: Cox
authors.forename: Lihadh
authors.initials: L
authors.lastname: Algazali
authors.forename: Richard C
authors.initials: RC
authors.lastname: Trembath
authors.forename: Vicente E
authors.initials: VE
authors.lastname: Torres
authors.forename: Tania
authors.initials: T
authors.lastname: Attie-Bitach
authors.forename: Deirdre A
authors.initials: DA
authors.lastname: Kelly
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
authors.forename: Vincent H
authors.initials: VH
authors.lastname: Gattone
authors.forename: Peter C
authors.initials: PC
authors.lastname: Harris
authors.forename: Colin A
authors.initials: CA
authors.lastname: Johnson
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005091:Exons / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009436:Neural Tube Defects / Q000235:genetics; D010375:Pedigree; D020161:Physical Chromosome Mapping; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains / Q000235:genetics*; D017208:Rats, Wistar; D013577:Syndrome
chemical_list: D005819:Genetic Markers; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C468846:TMEM67 protein, human