Autosomal recessive ADCY5-Related dystonia and myoclonus: Expanding the genetic spectrum of ADCY5-Related movement disorders
| Autor: | Amr M. Al-Saif, Brian F. Meyer, Hussam Abou-Al-Shaar, Edward Cupler, Saeed Bohlega, Balsam S. Bohlega, Huda Alajlan, Amaal AlDakheel, Dorota Monies |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Myoclonus Adolescent Genotype Mutation Missense Biology 03 medical and health sciences Young Adult 0302 clinical medicine medicine Missense mutation Humans Child Exome sequencing Genetic Association Studies Dystonia Genetics ADCY5 Movement Disorders Chorea Disease gene identification medicine.disease Pedigree 030104 developmental biology Neurology Female Neurology (clinical) Geriatrics and Gerontology medicine.symptom Hyperkinesia 030217 neurology & neurosurgery Adenylyl Cyclases |
| Zdroj: | Parkinsonismrelated disorders. 64 |
| ISSN: | 1873-5126 |
| Popis: | Introduction ADCY5-related hyperkinesia encompasses a heterogeneous group of phenotypes, including paroxysmal chorea, myoclonus, and dystonia. The disease is attributed to mutations of ADCY5, which encodes an adenylate cyclase enzyme. The disease can occur in a sporadic or familial pattern. With exception of one study, all reports on familial ADCY5-related hyperkinesia were associated with an autosomal dominant inheritance. Herein, we describe a native Arabian Bedouin family with an autosomal recessive ADCY5-related disorder and expand the genotypic and phenotypic spectrum of this disorder. Methods The pedigree included 4 generations of a family with 6 affected individuals. The patients were examined clinically and radiologically. Homozygosity mapping and Whole Exome Sequencing (WES) were used to identify a variant, predicted to be pathogenic, which segregated with disease in this family. Results All patients presented with early-onset dystonia and myoclonus. The patients had delayed motor and language milestones, axial hypotonia, severe anxiety, social phobia, and isolation. One patient had dilated cardiomyopathy. WES of one affected individual revealed a novel homozygous missense mutation (c.1762G > A, p.D588N) of ADCY5, that segregated with disease in an autosomal recessive manner, and was absent in more than 1000 ethnically-matched chromosomes. The mutation replaces a highly conserved nucleotide and is predicted to be deleterious. Conclusion This study reports the second family with autosomal recessive childhood-onset ADCY5-related disorder and expands our understanding of phenotype/genotype correlations of this disorder. |
| Databáze: | OpenAIRE |
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