title: Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation.
abstract: Patients with Joubert syndrome 2 (JBTS2) suffer from a neurological disease manifested by psychomotor retardation, hypotonia, ataxia, nystagmus, and oculomotor apraxia and variably associated with dysmorphism, as well as retinal and renal involvement. Brain MRI results show cerebellar vermis hypoplasia and additional anomalies of the fourth ventricle, corpus callosum, and occipital cortex. The disease has previously been mapped to the centromeric region of chromosome 11. Using homozygosity mapping in 13 patients from eight Ashkenazi Jewish families, we identified a homozygous mutation, R12L, in the TMEM216 gene, in all affected individuals. Thirty individuals heterozygous for the mutation were detected among 2766 anonymous Ashkenazi Jews, indicating a carrier rate of 1:92. Given the small size of the TMEM216 gene relative to other JBTS genes, its sequence analysis is warranted in all JBTS patients, especially those who suffer from associated anomalies.
authors.affiliation: Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Simon
authors.initials: S
authors.lastname: Edvardson
authors.forename: Avraham
authors.initials: A
authors.lastname: Shaag
authors.forename: Shamir
authors.initials: S
authors.lastname: Zenvirt
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Erlich
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
authors.forename: Alan L
authors.initials: AL
authors.lastname: Shanske
authors.forename: John Moshe
authors.initials: JM
authors.lastname: Gomori
authors.forename: Joseph
authors.initials: J
authors.lastname: Ekstein
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D006720:Homozygote; D006801:Humans; D007223:Infant; D007585:Jews; D008279:Magnetic Resonance Imaging / Q000379:methods; D009154:Mutation; D009422:Nervous System Diseases / Q000208:ethnology / Q000235:genetics*; D013577:Syndrome