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Whole exome sequencing identified a novel missense alteration in CC2D2A causing Joubert syndrome 9 in a Pakhtun family
- Source :
- The journal of gene medicineREFERENCES. 23(1)
- Publication Year :
- 2020
-
Abstract
- Background Joubert syndrome (JBTS) is a heterogenous disorder characterized by intellectual disability, developmental delays, molar tooth sign in brain imaging, hypotonia, ocular motor apraxia and overlapping features of ciliopathies. There are 36 clinical subtypes of JBTS, with an equal number of genes known so far for this phenotype. Methods Whole exome sequencing (WES) and Sanger sequencing were performed for the molecular diagnosis of a Pakhtun family affected with Joubert syndrome type 9 (JBTS9). Results A novel homozygous missense variant (c.4417C>G; Pro1473Ala) in exon 34 was identified in coiled-coil and C2 domains-containing the protein 2A (CC2D2A; NM_001080522) gene. The variant co-segregated in autosomal recessive fashion within the family and was not found in 200 ethnically matched unaffected individuals. In silico analyses supported the pathogenic effect of the altered CC2D2A protein. Conclusions To the best of our knowledge, this is the first report of CC2D2A alteration co-segragating with a JBTS9 phenotype in a Pakhtun family from Pakistan. Our findings broaden the pathogenic spectrum of JBTS9, adding a novel variant to CC2D2A variation pool. WES analysis is a successful molecular diagnostic tool for rare genetic disorders, especially in those populations where the marriage of cousins is more frequent. Efficient and accurate genetic testing and counselling of the affected families are helpful for patient management and for reducing the disease burden in future generations.
- Subjects :
- 0301 basic medicine
Adult
Male
Genotype
DNA Mutational Analysis
Mutation, Missense
Biology
CC2D2A
Ciliopathies
Joubert syndrome
03 medical and health sciences
symbols.namesake
Consanguinity
0302 clinical medicine
Cerebellar Diseases
Intellectual Disability
Drug Discovery
Exome Sequencing
Genetics
medicine
Missense mutation
Humans
Genetic Predisposition to Disease
Eye Abnormalities
Molecular Biology
Genetics (clinical)
Exome sequencing
Alleles
Genetic Association Studies
Genetic testing
Sanger sequencing
medicine.diagnostic_test
Computational Biology
medicine.disease
Hypotonia
Pedigree
Cytoskeletal Proteins
030104 developmental biology
Phenotype
030220 oncology & carcinogenesis
symbols
Molecular Medicine
Female
Kidney Diseases
medicine.symptom
Subjects
Details
- ISSN :
- 15212254
- Volume :
- 23
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- The journal of gene medicineREFERENCES
- Accession number :
- edsair.doi.dedup.....eb1cd3a8a86d1e1de08d45708a713952