title: Clinical and molecular effect on offspring of a marriage of consanguineous spinocerebellar ataxia type 7 mutation carriers: a family case report.
abstract: Spinocerebellar ataxia type 7 (SCA7) is a genetic disorder characterized by degeneration of the cerebellum, brainstem, and retina that is caused by abnormal expansion of a CAG repeat located in the ATXN7 gene encoding sequence on chromosome 3p21.1. Although SCA7 is an uncommon autosomal dominant ataxia, we previously found increased prevalence of the disease in a Southeastern Mexican population. In this study, we described to our knowledge for the first time a marriage of consanguineous SCA7 mutation carriers and their offspring effect. We characterized a severely affected infantile-onset female patient whose parents and two siblings exhibited no symptoms of the disease at time of diagnosis. A comprehensive clinical analysis of the proband showed a progressive cerebellar syndrome, including gait ataxia, movement disorders, and saccadic movements, as well as hyperreflexia, visual deterioration, urinary and cardiovascular dysfunction, and impaired nerve conduction. The SCA7 mutation was detected in the proband patient. Subsequently, genetic examination using four ATXN7 gene-linked markers (three centromeric microsatellite markers [D3S1228, D3S1287, and D3S3635] and an intragenic Single Nucleotide Polymorphism [SNP-3145G/A]) revealed that the proband descends from a couple of consanguineous SCA7 mutation carriers. Genotyping analysis demonstrated that all offspring inherited only one mutant allele, and that the severe infantile-onset phenotype is caused by germinal expansion (from 37 to 72 CAG repeats) of the paternal mutant allele. Interestingly, the couple also referred a miscarriage. Finally, we found no CAA interruptions in the ATXN7 gene CAG repeats tract in this family, which might explain, at least in part, the triplet instability in the proband.
authors: Department of Genetics Laboratory of Genomic Medicine, National Rehabilitation Institute (INR) Mexico City, Mexico.
authors: Jonathan J
authors: JJ
authors: Magaña
authors: Department of Genetics Laboratory of Genomic Medicine, National Rehabilitation Institute (INR) Mexico City, Mexico.
authors: Yessica S
authors: YS
authors: Tapia-Guerrero
authors: Department of Genetics Laboratory of Genomic Medicine, National Rehabilitation Institute (INR) Mexico City, Mexico ; Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (CINVESTAV)-IPN Mexico City, Mexico ; Center for Research and Rehabilitation of The Hereditary Ataxias (CIRAH) Holguín, Cuba.
authors: Luis
authors: L
authors: Velázquez-Pérez
authors: Center for Research and Rehabilitation of The Hereditary Ataxias (CIRAH) Holguín, Cuba.
authors: Tania
authors: T
authors: Cruz-Mariño
authors: Department of Genetics Laboratory of Genomic Medicine, National Rehabilitation Institute (INR) Mexico City, Mexico ; Rehabilitation and Social Inclusion Center of Veracruz (CRIS-DIF) Xalapa, Veracruz, Mexico.
authors: Cesar M
authors: CM
authors: Cerecedo-Zapata
authors: Department of Toxicology, CINVESTAV-IPN Mexico City, Mexico.
authors: Rocío
authors: R
authors: Gómez
authors: Department of Genetics Laboratory of Genomic Medicine, National Rehabilitation Institute (INR) Mexico City, Mexico.
authors: Nadia M
authors: NM
authors: Murillo-Melo
authors: Department of Neurosciences, INR Mexico City, Mexico.
authors: Rigoberto
authors: R
authors: González-Piña
authors: Department of Genetics Laboratory of Genomic Medicine, National Rehabilitation Institute (INR) Mexico City, Mexico.
authors: Oscar
authors: O
authors: Hernández-Hernández
authors: Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (CINVESTAV)-IPN Mexico City, Mexico.
authors: Bulmaro
authors: B
authors: Cisneros
keywords: CAA interruptions; CAG repeats; consanguineous marriage; electrophysiological findings; infantile-onset phenotype; intergenerational transmission; spinocerebellar ataxia type 7