In:
Annals of Neurology, Wiley, Vol. 59, No. 3 ( 2006-03), p. 527-534
Abstract:
Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. It is characterized by hypoplasia of the cerebellar vermis and a particular midbrain‐hindbrain “molar tooth” sign, a finding shared by a group of Joubert syndrome–related disorders (JSRDs), with wide phenotypic variability. The frequency of mutations in the first positionally cloned gene, AHI1 , is unknown. Methods We searched for mutations in the AHI1 gene among a cohort of 137 families with JSRD and radiographically proven molar tooth sign. Results We identified 15 deleterious mutations in 10 families with pure JS or JS plus retinal and/or additional central nervous system abnormalities. Mutations among families with JSRD including kidney or liver involvement were not detected. Transheterozygous mutations were identified in the majority of those without history of consanguinity. Most mutations were truncating or splicing errors, with only one missense mutation in the highly conserved WD40 repeat domain that led to disease of similar severity. Interpretation AHI1 mutations are a frequent cause of disease in patients with specific forms of JSRD. Ann Neurol 2006
Type of Medium:
Online Resource
ISSN:
0364-5134
,
1531-8249
Language:
English
Publisher:
Wiley
Publication Date:
2006
detail.hit.zdb_id:
80362-5
detail.hit.zdb_id:
2037912-2
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