Molecular characterization of Joubert syndrome in Saudi Arabia

Anas M Alazami; Muneera J Alshammari; Mustafa A Salih; Fatema Alzahrani; Hadia Hijazi; Mohammed Z Seidahmed; Leen Abu Safieh; Mazhor Aldosary; Arif O Khan; Fowzan S Alkuraya

doi:10.1002/humu.22134

Molecular characterization of Joubert syndrome in Saudi Arabia

Hum Mutat. 2012 Oct;33(10):1423-8. doi: 10.1002/humu.22134. Epub 2012 Jul 11.

Authors

Anas M Alazami¹, Muneera J Alshammari, Mustafa A Salih, Fatema Alzahrani, Hadia Hijazi, Mohammed Z Seidahmed, Leen Abu Safieh, Mazhor Aldosary, Arif O Khan, Fowzan S Alkuraya

Affiliation

¹ Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

PMID: 22693042
DOI: 10.1002/humu.22134

Abstract

Joubert syndrome (JS) is a ciliopathy that is defined primarily by typical cerebellar structural and ocular motility defects. The genetic heterogeneity of this condition is significant with 16 genes identified to date. We have used a combination of autozygome-guided candidate gene mutation analysis and exome sequencing to identify the causative mutation in a series of 12 families. The autozygome approach identified mutations in RPGRIP1L, AHI1, TMEM237, and CEP290, while exome sequencing revealed families with truncating mutations in TCTN1 and C5ORF42. Our study, the largest comprehensive molecular series on JS, provides independent confirmation of the recently reported TCTN1, TMEM237, and C5ORF42 as bona fide JS disease genes, and expands the allelic heterogeneity of this disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Abnormalities, Multiple
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Adaptor Proteins, Vesicular Transport
Antigens, Neoplasm / genetics
Antigens, Neoplasm / metabolism
Cell Cycle Proteins
Cerebellar Diseases / ethnology
Cerebellar Diseases / genetics*
Cerebellum / abnormalities
Child
Child, Preschool
Cytoskeletal Proteins
Exome / genetics
Eye Abnormalities / ethnology
Eye Abnormalities / genetics*
Female
Genetic Association Studies
Humans
Infant
Kidney Diseases, Cystic / ethnology
Kidney Diseases, Cystic / genetics*
Membrane Proteins / genetics
Membrane Proteins / metabolism
Mutation
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism
Pedigree
Retina / abnormalities
Saudi Arabia

Substances

AHI1 protein, human
Adaptor Proteins, Signal Transducing
Adaptor Proteins, Vesicular Transport
Antigens, Neoplasm
Cell Cycle Proteins
Cep290 protein, human
Cytoskeletal Proteins
Membrane Proteins
Neoplasm Proteins
RPGRIP1L protein, human
TMEM237 protein, human

Supplementary concepts

Agenesis of Cerebellar Vermis