Molecular characterization of Joubert syndrome in Saudi Arabia.
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.
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Anas M
AM
Alazami
Muneera J
MJ
Alshammari
Mustafa A
MA
Salih
Fatema
F
Alzahrani
Hadia
H
Hijazi
Mohammed Z
MZ
Seidahmed
Leen
L
Abu Safieh
Mazhor
M
Aldosary
Arif O
AO
Khan
Fowzan S
FS
Alkuraya
D000015:Abnormalities, Multiple; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002526:Cerebellar Diseases / Q000208:ethnology / Q000235:genetics*; D002531:Cerebellum / Q000002:abnormalities; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins; D059472:Exome / Q000235:genetics; D005124:Eye Abnormalities / Q000208:ethnology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D052177:Kidney Diseases, Cystic / Q000208:ethnology / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D012160:Retina / Q000002:abnormalities; D012529:Saudi Arabia
C487178:AHI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C532826:RPGRIP1L protein, human; C569629:TMEM237 protein, human