A homozygous AHI1 gene mutation (p.Thr304AsnfsX6) in a consanguineous Moroccan family with Joubert syndrome: a case report
| Autor: | Matthias Chalon, Tania Attié-Bitach, Maria Mansouri, Siham Chafai-Elalaoui, Yamna Kriouele, Nadia Elkhartoufi, Lekbir Baala, Abdelaziz Sefiani |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Pathology medicine.medical_specialty Heterozygote Adolescent Gene mutation Compound heterozygosity Joubert syndrome Retina Homozygosity mapping Cerebellar Diseases Cerebellum medicine Humans Abnormalities Multiple Eye Abnormalities Child Adaptor Proteins Signal Transducing Medicine(all) Genetic heterogeneity business.industry General Medicine Kidney Diseases Cystic medicine.disease Disease gene identification Magnetic Resonance Imaging Hypotonia eye diseases Pedigree Ciliopathy Adaptor Proteins Vesicular Transport Morocco AHI1 mutation Mutation Female medicine.symptom business Congenital disorder Research Article |
| Zdroj: | Journal of Medical Case Reports |
| ISSN: | 1752-1947 |
| Popis: | Introduction Joubert syndrome is a rare congenital disorder characterized by brain malformation, developmental delay with hypotonia, ocular motor apraxia, and breathing abnormalities. Joubert syndrome is a genetically highly heterogeneous ciliopathy disorder with 23 identified causative genes. The diagnosis is based on brain imaging showing the “molar tooth sign” with cerebellar vermis agenesis. We describe a consanguineous Moroccan family with three affected siblings (18-year-old boy, 13-year-old girl, and 10-year-old boy) showing typical signs of Joubert syndrome, and attempt to identify the underlying genetic defect in this family. Methods We performed genome-wide homozygosity mapping using a high-resolution array followed by targeted Sanger sequencing to identify the causative gene. Results This approach found three homozygous regions, one including the AHI1 gene. Direct sequencing of the 26 coding exons of AHI1 revealed a homozygous mutation (p.Thr304AsnfsX6) located in exon 7 present in the three Joubert syndrome-affected Moroccan siblings. Of more interest, this truncating mutation was previously reported in patients with compound heterozygous Joubert syndrome originating from Spain (one patient) and from the Netherlands (two patients), suggesting a possible founder effect or mutational hotspot. Conclusions Combined homozygosity mapping and targeted sequencing allowed the rapid detection of the disease-causing mutation in the AHI1 gene in this family affected with a highly genetically heterogeneous disorder. Carriers of the same truncating mutation (p.Thr304AsnfsX6), originating from Spain and the Netherlands, presented variable clinical characteristics, thereby corroborating the extreme heterogeneity of Joubert syndrome. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|