Dataset Information

ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations.

ABSTRACT: To investigate the clinical spectrum and distinguishing features of adenylate cyclase 5 (ADCY5)-related dyskinesia and genotype-phenotype relationship.We analyzed ADCY5 in patients with choreiform or dystonic movements by exome or targeted sequencing. Suspected mosaicism was confirmed by allele-specific amplification. We evaluated clinical features in our 50 new and previously reported cases.We identified 3 new families and 12 new sporadic cases with ADCY5 mutations. These mutations cause a mixed hyperkinetic disorder that includes dystonia, chorea, and myoclonus, often with facial involvement. The movements are sometimes painful and show episodic worsening on a fluctuating background. Many patients have axial hypotonia. In 2 unrelated families, a p.A726T mutation in the first cytoplasmic domain (C1) causes a relatively mild disorder of prominent facial and hand dystonia and chorea. Mutations p.R418W or p.R418Q in C1, de novo in 13 individuals and inherited in 1, produce a moderate to severe disorder with axial hypotonia, limb hypertonia, paroxysmal nocturnal or diurnal dyskinesia, chorea, myoclonus, and intermittent facial dyskinesia. Somatic mosaicism is usually associated with a less severe phenotype. In one family, a p.M1029K mutation in the C2 domain causes severe dystonia, hypotonia, and chorea. The progenitor, whose childhood-onset episodic movement disorder almost disappeared in adulthood, was mosaic for the mutation.ADCY5-related dyskinesia is a childhood-onset disorder with a wide range of hyperkinetic abnormal movements. Genotype-specific correlations and mosaicism play important roles in the phenotypic variability. Recurrent mutations suggest particular functional importance of residues 418 and 726 in disease pathogenesis.

SUBMITTER: Chen DH

PROVIDER: S-EPMC4676753 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations.

Chen Dong-Hui DH Méneret Aurélie A Friedman Jennifer R JR Korvatska Olena O Gad Alona A Bonkowski Emily S ES Stessman Holly A HA Doummar Diane D Mignot Cyril C Anheim Mathieu M Bernes Saunder S Davis Marie Y MY Damon-Perrière Nathalie N Degos Bertrand B Grabli David D Gras Domitille D Hisama Fuki M FM Mackenzie Katherine M KM Swanson Phillip D PD Tranchant Christine C Vidailhet Marie M Winesett Steven S Trouillard Oriane O Amendola Laura M LM Dorschner Michael O MO Weiss Michael M Eichler Evan E EE Torkamani Ali A Roze Emmanuel E Bird Thomas D TD Raskind Wendy H WH

Neurology 20151104 23

<h4>Objective</h4>To investigate the clinical spectrum and distinguishing features of adenylate cyclase 5 (ADCY5)-related dyskinesia and genotype-phenotype relationship.<h4>Methods</h4>We analyzed ADCY5 in patients with choreiform or dystonic movements by exome or targeted sequencing. Suspected mosaicism was confirmed by allele-specific amplification. We evaluated clinical features in our 50 new and previously reported cases.<h4>Results</h4>We identified 3 new families and 12 new sporadic cases ...[more]

PMID: 26537056

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Dataset Information

ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations.

Publications

ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations.

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