RESUMO
BACKGROUND: Autosomal dominant cerebellar ataxia, currently denominated spinocerebellar ataxia (SCAs), represents a heterogeneous group of neurodegenerative disorders affecting the cerebellum and its connections. We describe the clinical and molecular findings in 16 patients originating from Malian families, who suffer from progressive cerebellar ataxia syndrome. METHODS AND RESULTS: Molecular analysis allows genetic profiles of SCA to be distinguished. In seven patients, SCA type 2 (CAG) mutation was expanded from 39 to 43 repeats. SCA type 7 (CAG) mutation was confirmed in six patients. Mutations were expanded from 49 to 59 repeats. In three patients, SCA type3 was diagnosed and CAG mutation was expanded to 73 repeats. CONCLUSIONS: Our data suggest that the most frequent types of SCA are SCA2 and SCA7. However, further studies are needed to confirm these preliminary results.
Assuntos
Predisposição Genética para Doença/genética , Mutação/genética , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética , Expansão das Repetições de Trinucleotídeos/genética , Adulto , Idoso , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Mali/epidemiologia , Pessoa de Meia-Idade , Ataxias Espinocerebelares/classificaçãoRESUMO
We identified a family in Mali with two sisters affected by spastic paraplegia. In addition to spasticity and weakness of the lower limbs, the patients had marked atrophy of the distal upper extremities. Homozygosity mapping using single nucleotide polymorphism arrays showed that the sisters shared a region of extended homozygosity at chromosome 19p13.11-q12 that was not shared by controls. These findings indicate a clinically and genetically distinct form of hereditary spastic paraplegia with amyotrophy, designated SPG43.
Assuntos
Neurite do Plexo Braquial/genética , Cromossomos Humanos Par 19/genética , Loci Gênicos , Paraplegia Espástica Hereditária/genética , Adolescente , Idade de Início , Feminino , Homozigoto , Humanos , Mali , Linhagem , Polimorfismo de Nucleotídeo Único , Irmãos , Adulto JovemRESUMO
We studied a Malian family with parental consanguinity and two of eight siblings affected with late-childhood-onset progressive myoclonus epilepsy and cognitive decline, consistent with the diagnosis of Lafora disease. Genetic analysis showed a novel homozygous single-nucleotide variant in the NHLRC1 gene, c.560A>C, producing the missense change H187P. The changed amino acid is highly conserved, and the mutation impairs malin's ability to degrade laforin in vitro. Pathological evaluation showed manifestations of Lafora disease in the entire brain, with particularly severe involvement of the pallidum, thalamus, and cerebellum. Our findings document Lafora disease with severe manifestations in the West African population.
