Expanding the ADCY5 phenotype toward spastic paraparesis: Amutation in the M2 domain
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Patients with an ADCY5 gene mutation reveal a heterogenous clinical presentation including axial hypotonia, motor milestone delay, fluctuating dyskinesias, dystonia, and/or myoclonus with episodic exacerbations during drowsiness and sleep.1,2 Phenotype-genotype correlations and somatic mosaicism are suggested to explain the wide phenotypic spectrum.1 The ADCY5 gene encodes 1 of 9 membrane-bound adenyl cyclases converting adenosine triphosphate to cyclic adenosine-39, 59-monophosphate, the second messenger in a range of cellular activities.3 The ADCY5 protein contains 2 transmembrane domains, M1 and M2, and 2 bipartite cytoplasmic domains, C1 and C2. Pathogenic mutations have been described in domains C1 and C2.1,2 Mutations are likely to have a gain-of-function effect based on increased cyclic adenosine-39, 59-monophosphate accumulation.4 The present report describes 3 cases of ADCY5 dyskinesia to further illustrate the clinical spectrum: a new phenotype, i.e., spastic paraparesis due to a mutation located in the M2 domain; case 1, case 2, and case 3 show previously described mutations in the C1 domain of the ADCY5 protein. Their phenotypes show important similarities to previous cases, with the addition of the psychiatric symptoms of the patient in case 3.
Ämnesklassifikation (UKÄ) – OBLIGATORISK
|Status||Published - 2018 feb|
|Peer review utförd||Ja|