Expanding the ADCY5 phenotype toward spastic paraparesis: Amutation in the M2 domain

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Expanding the ADCY5 phenotype toward spastic paraparesis : Amutation in the M2 domain. / Waalkens, Anne J.E.; Vansenne, Fleur; Van Der Hout, Annemarie H.; Zutt, Rodi; Mourmans, Jeroen; Tolosa, Eduardo; De Koning, Tom J.; Tijssen, Marina A.J.

In: Neurology: Genetics, Vol. 4, No. 1, e214, 02.2018.

Research output: Contribution to journalArticle

Harvard

Waalkens, AJE, Vansenne, F, Van Der Hout, AH, Zutt, R, Mourmans, J, Tolosa, E, De Koning, TJ & Tijssen, MAJ 2018, 'Expanding the ADCY5 phenotype toward spastic paraparesis: Amutation in the M2 domain', Neurology: Genetics, vol. 4, no. 1, e214. https://doi.org/10.1212/NXG.0000000000000214

APA

Waalkens, A. J. E., Vansenne, F., Van Der Hout, A. H., Zutt, R., Mourmans, J., Tolosa, E., De Koning, T. J., & Tijssen, M. A. J. (2018). Expanding the ADCY5 phenotype toward spastic paraparesis: Amutation in the M2 domain. Neurology: Genetics, 4(1), [e214]. https://doi.org/10.1212/NXG.0000000000000214

CBE

Waalkens AJE, Vansenne F, Van Der Hout AH, Zutt R, Mourmans J, Tolosa E, De Koning TJ, Tijssen MAJ. 2018. Expanding the ADCY5 phenotype toward spastic paraparesis: Amutation in the M2 domain. Neurology: Genetics. 4(1):Article e214. https://doi.org/10.1212/NXG.0000000000000214

MLA

Vancouver

Waalkens AJE, Vansenne F, Van Der Hout AH, Zutt R, Mourmans J, Tolosa E et al. Expanding the ADCY5 phenotype toward spastic paraparesis: Amutation in the M2 domain. Neurology: Genetics. 2018 Feb;4(1). e214. https://doi.org/10.1212/NXG.0000000000000214

Author

Waalkens, Anne J.E. ; Vansenne, Fleur ; Van Der Hout, Annemarie H. ; Zutt, Rodi ; Mourmans, Jeroen ; Tolosa, Eduardo ; De Koning, Tom J. ; Tijssen, Marina A.J. / Expanding the ADCY5 phenotype toward spastic paraparesis : Amutation in the M2 domain. In: Neurology: Genetics. 2018 ; Vol. 4, No. 1.

RIS

TY - JOUR

T1 - Expanding the ADCY5 phenotype toward spastic paraparesis

T2 - Amutation in the M2 domain

AU - Waalkens, Anne J.E.

AU - Vansenne, Fleur

AU - Van Der Hout, Annemarie H.

AU - Zutt, Rodi

AU - Mourmans, Jeroen

AU - Tolosa, Eduardo

AU - De Koning, Tom J.

AU - Tijssen, Marina A.J.

PY - 2018/2

Y1 - 2018/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85048702231&partnerID=8YFLogxK

U2 - 10.1212/NXG.0000000000000214

DO - 10.1212/NXG.0000000000000214

M3 - Article

AN - SCOPUS:85048702231

VL - 4

JO - Neurology. Genetics

JF - Neurology. Genetics

SN - 2376-7839

IS - 1

M1 - e214

ER -