Identification of a new homozygous CEP290 gene mutation in a Saudi family causing Joubert syndrome using next-generation sequencing

• Published in: Saudi journal of kidney diseases and transplantation 2019-07, Vol.30 (4), p.964-968
• Main Authors: Khamis, Khamis, Abd al-Qadir, al-Badri, al-Sahlawi, Muthanna, al-Turki, Lulwah, Ahmad, Wasim
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - genetics; Abnormalities, Multiple - therapy; Antigens, Neoplasm - genetics; Ataxia; Cell Cycle Proteins - genetics; Cerebellum - abnormalities; Chromosomes; Chronic kidney failure; Cognitive ability; Cytoskeletal Proteins - genetics; Diagnosis; Diagnostic imaging; DNA Mutational Analysis - methods; Eye Abnormalities - diagnosis; Eye Abnormalities - genetics; Eye Abnormalities - therapy; Eye movements; Female; Gene mutation; Genes; Genetic Predisposition to Disease; Hepatitis; Heterozygote; High-Throughput Nucleotide Sequencing; Homeostasis; Humans; Joubert syndrome; Kidney diseases; Kidney Diseases, Cystic - diagnosis; Kidney Diseases, Cystic - genetics; Kidney Diseases, Cystic - therapy; Laboratories; Magnetic resonance imaging; Mutation; Nystagmus; Parents & parenting; Patients; Phenotype; Predictive Value of Tests; Prognosis; Proteins; Retina - abnormalities; Risk Factors; Saudi Arabia; Twins; Urine; Young Adult; التشخيص; الجوانب الجزيئية; الطفرة; المرضى; متلازمة جوبيرت
• ISSN: 1319-2442; 2320-3838
• DOI: 10.4103/1319-2442.265475

A 19-year-old female with a learning difficulty, ataxia, and nystagmus was referred to our clinic with advanced chronic kidney disease. Her renal biopsy revealed features of nephronophthisis (NPHP). Magnetic resonance imaging of the brain showed “molar tooth sign.” The clinical picture was consistent with Joubert syndrome (JS). Two of her siblings were subsequently found to have a similar condition. Genomic material from the patient, her twin sister, and later on from parents was analyzed for deletion/duplication mutations in the NPHP1 gene using multiplex ligation-dependent probe amplification. No genetic defect was discerned. However, applying the emerging “Next-Generation Sequencing (NGS)” method, we identified a novel c.5704G>T mutation in exon 41 of the CEP290 gene on chromosome 12q21. The identification of this novel mutation, that is, highly likely to be pathogenic was compatible with the diagnosis of JS. This mutation may be included in screening and diagnostic panel. NGS provides an excellent screening method for genetic testing.