title: The Meckel-Gruber syndrome gene, MKS3, is mutated in Joubert syndrome.
abstract: Joubert syndrome (JS) is an autosomal recessive disorder characterized by cerebellar vermis hypoplasia associated with hypotonia, developmental delay, abnormal respiratory patterns, and abnormal eye movements. The association of retinal dystrophy and renal anomalies defines JS type B. JS is a genetically heterogeneous condition with mutations in two genes, AHI1 and CEP290, identified to date. In addition, NPHP1 deletions identical to those that cause juvenile nephronophthisis have been identified in a subset of patients with a mild form of cerebellar and brainstem anomaly. Occipital encephalocele and/or polydactyly have occasionally been reported in some patients with JS, and these phenotypic features can also be observed in Meckel-Gruber syndrome (MKS). MKS is a rare, autosomal recessive lethal condition characterized by central nervous system malformations (typically, occipital meningoencephalocele), postaxial polydactyly, multicystic kidney dysplasia, and ductal proliferation in the portal area of the liver. Since there is obvious phenotypic overlap between JS and MKS, we hypothesized that mutations in the recently identified MKS genes, MKS1 on chromosome 17q and MKS3 on 8q, may be a cause of JS. After mutation analysis of MKS1 and MKS3 in a series of patients with JS (n=22), we identified MKS3 mutations in four patients with JS, thus defining MKS3 as the sixth JS locus (JBTS6). No MKS1 mutations were identified in this series, suggesting that the allelism is restricted to MKS3.
authors.affiliation: INSERM U-781, Hopital Necker-Enfants Malades, Paris, France.
authors.forename: Lekbir
authors.initials: L
authors.lastname: Baala
authors.forename: Stephane
authors.initials: S
authors.lastname: Romano
authors.forename: Rana
authors.initials: R
authors.lastname: Khaddour
authors.forename: Sophie
authors.initials: S
authors.lastname: Saunier
authors.forename: Ursula M
authors.initials: UM
authors.lastname: Smith
authors.forename: Sophie
authors.initials: S
authors.lastname: Audollent
authors.forename: Catherine
authors.initials: C
authors.lastname: Ozilou
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Nicole
authors.initials: N
authors.lastname: Laurent
authors.forename: Bernard
authors.initials: B
authors.lastname: Foliguet
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Remi
authors.initials: R
authors.lastname: Salomon
authors.forename: Ferechte
authors.initials: F
authors.lastname: Encha-Razavi
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gubler
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
authors.forename: Colin A
authors.initials: CA
authors.lastname: Johnson
authors.forename: Michel
authors.initials: M
authors.lastname: Vekemans
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.forename: Tania
authors.initials: T
authors.lastname: Attie-Bitach
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D001921:Brain / Q000002:abnormalities; D002531:Cerebellum / Q000473:pathology; D002648:Child; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005260:Female; D005333:Fetus / Q000002:abnormalities; D006801:Humans; D007668:Kidney / Q000002:abnormalities; D008099:Liver / Q000002:abnormalities; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D011247:Pregnancy; D011506:Proteins / Q000235:genetics; D013577:Syndrome
chemical_list: C509165:MKS1 protein, human; D008565:Membrane Proteins; D011506:Proteins; C468846:TMEM67 protein, human