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. 2010 Jan;86(1):93-7.
doi: 10.1016/j.ajhg.2009.12.007. Epub 2009 Dec 31.

Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation

Simon Edvardson  1 , Avraham Shaag, Shamir Zenvirt, Yaniv Erlich, Gregory J Hannon, Alan L Shanske, John Moshe Gomori, Joseph Ekstein, Orly Elpeleg
Affiliations

Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation

Simon Edvardson et al. Am J Hum Genet. 2010 Jan.

Erratum in

  • Am J Hum Genet. 2010 Feb;86(2):294. Shanske, Alan L [added]

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.

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Figures

Figure 1
Figure 1
Magnetic Resonance Images of the Patients, Illustrating the Typical Anomalies (A and B) Axial T2-weighted images showing (A) a completely absent vermis with a wide space between the cerebellar hemispheres (arrow) and (B) a dysplastic split vermis (arrow) without an opening or separation of the cerebellar hemispheres. (C) Midsagittal T1-weighted image showing cystic dilatation of the fourth ventricle (arrow) and vermian hypoplasia.
Figure 2
Figure 2
The Homozygous Regions and the TMEM216 Mutation (A) Homozygous regions of the six SNP-genotyped patients (blue rectangles) within the chromosome 11 centromeric region. (B) Chromatograms showing the sequence of exon 3, the first coding exon, of the TMEM216 gene. 1, a normal control;. 2, a patient homozygous for the c.35G>T mutation (arrow); 3, an obligatory carrier of the mutation.
See this image and copyright information in PMC

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