title: Novel CC2D2A compound heterozygous mutations cause Joubert syndrome.
abstract: Joubert syndrome (JS) is an autosomal recessive disorder, which is characterized by hypotonia, ataxia, psychomotor delay, and variable occurrences of oculomotor apraxia and neonatal breathing abnormalities. JS is clinically and genetically heterogeneous. The present study investigated a typical JS family. The 'molar tooth sign' was observed in the proband through magnetic resonance imaging. Other symptoms of JS include cerebellar vermis hypoplasia/dysplasia, oculomotor apraxia and intellectual disability. High‑throughput sequencing revealed that JS was caused by coiled‑coil and C2 domain containing 2A (CC2D2A) compound heterozygous mutations. One CC2D2A allele was affected with a missense mutation, c.2581G>A, which led to a p.Asp861Asn amino acid replacement. The other allele was affected with a c.2848C>T nonsense mutation, which resulted in a truncated CC2D2A protein (p.Arg950Ter). Both of these alterations are novel. Further investigation indicated that the proband's father was the c.2581G>A carrier, whereas the mother was the c.2848C>T carrier. These results indicated that JS in the proband was caused by novel compound heterozygous mutations in CC2D2A, which were inherited from both parents. These findings may be used to establish prenatal molecular diagnostic criteria, which may be beneficial in future pregnancies.
authors.affiliation: Clinical Laboratory, Zunyi Medical University Affiliated Hospital, Zunyi, Guizhou 563099, P.R. China.
authors.forename: Daimin
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Clinical Laboratory, Zunyi Medical University Affiliated Hospital, Zunyi, Guizhou 563099, P.R. China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Lv
authors.affiliation: Department of Genetics, Zunyi Medical University, Zunyi, Guizhou 563099, P.R. China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Genetics, Zunyi Medical University, Zunyi, Guizhou 563099, P.R. China.
authors.forename: Mingsong
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Genetics, Zunyi Medical University, Zunyi, Guizhou 563099, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Genetics, Zunyi Medical University, Zunyi, Guizhou 563099, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Genetics, Zunyi Medical University, Zunyi, Guizhou 563099, P.R. China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Guan
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Jindong
authors.initials: J
authors.lastname: Chen
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D001933:Brain Stem / Q000000981:diagnostic imaging / Q000473:pathology; D002531:Cerebellum / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000473:pathology; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D052177:Kidney Diseases, Cystic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D012160:Retina / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: C528701:CC2D2A protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins