INTRODUCTION: @entity14475 is a rare @entity4670 characterized by @entity75 , @entity245 with @entity2421 , @entity24147 , and @entity1353 . @entity14475 is a genetically highly heterogeneous @entity74 with 23 identified causative genes. The diagnosis is based on brain imaging showing the "molar tooth sign" with @entity44999 . We describe a consanguineous Moroccan family with three affected siblings (18-year-old @entity1 , 13-year-old @entity1 , and 10-year-old @entity1 ) showing typical signs of @entity14475 , 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 @entity6394 gene. Direct sequencing of the 26 coding exons of @entity6394 revealed a homozygous mutation (p.Thr304AsnfsX6) located in exon 7 present in the three @entity14475 -affected Moroccan siblings. Of more interest, this truncating mutation was previously reported in @entity1 with compound heterozygous @entity14475 originating from Spain (one @entity1 ) and from the Netherlands (two @entity1 ), 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 @entity6394 gene in this family affected with a highly genetically heterogeneous disorder. Carriers of the same truncating mutation ( @entity69785 ), originating from Spain and the Netherlands, presented variable clinical characteristics, thereby corroborating the extreme heterogeneity of @entity14475 .

A homozygous @entity6394 gene mutation ( @entity69785 ) in a consanguineous Moroccan family with XXXX : a case report.

@entity1 :: ('9606', 'Species') :: ['girl', 'patients', 'patient', 'boy'] @entity4670 :: ('MESH:D009358', 'Disease') :: ['congenital disorder'] @entity1353 :: ('MESH:D004417', 'Disease') :: ['breathing abnormalities'] @entity75 :: ('MESH:D001927', 'Disease') :: ['brain malformation'] @entity14475 :: ('MESH:C536293', 'Disease') :: ['Joubert syndrome'] @entity69785 :: ('p|FS|T|304|N|6', 'ProteinMutation') :: ['p.Thr304AsnfsX6'] @entity245 :: ('MESH:D002658', 'Disease') :: ['developmental delay'] @entity44999 :: ('MESH:C580212', 'Disease') :: ['cerebellar vermis agenesis'] @entity2421 :: ('MESH:D009123', 'Disease') :: ['hypotonia'] @entity6394 :: ('54806', 'Gene') :: ['AHI1'] @entity74 :: ('MESH:D030342', 'Disease') :: ['ciliopathy disorder'] @entity24147 :: ('MESH:C537423', 'Disease') :: ['ocular motor apraxia']
@entity14475 :: (MESH:C536293,Disease) :: ['Joubert syndrome']
