RGD Reference Report - A homozygous AHI1 gene mutation (p.Thr304AsnfsX6) in a consanguineous Moroccan family with Joubert syndrome: a case report. - Rat Genome Database

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A homozygous AHI1 gene mutation (p.Thr304AsnfsX6) in a consanguineous Moroccan family with Joubert syndrome: a case report.

Authors: Chafai-Elalaoui, S  Chalon, M  Elkhartoufi, N  Kriouele, Y  Mansouri, M  Attie-Bitach, T  Sefiani, A  Baala, L 
Citation: Chafai-Elalaoui S, etal., J Med Case Rep. 2015 Nov 5;9:254. doi: 10.1186/s13256-015-0732-3.
RGD ID: 11343130
Pubmed: PMID:26541515   (View Abstract at PubMed)
PMCID: PMC4635607   (View Article at PubMed Central)
DOI: DOI:10.1186/s13256-015-0732-3   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Joubert syndrome 3  IAGP 11343130DNA:nonsense mutation:cds:c.910dup (human)RGD 
Joubert syndrome 3  ISOAHI1 (Homo sapiens)11343130; 11343130DNA:nonsense mutation:cds:c.910dup (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ahi1  (Abelson helper integration site 1)

Genes (Mus musculus)
Ahi1  (Abelson helper integration site 1)

Genes (Homo sapiens)
AHI1  (Abelson helper integration site 1)


Additional Information