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An atypical form of AOA2 with myoclonus associated with mutations in SETX and AFG3L2

Mancini, C and Orsi, L and Guo, Y and Li, J and Chen, Y and Wang, F and Tian, L and Liu, X and Zhang, J and Jiang, H and Nmezi, BS and Tatsuta, T and Giorgio, E and Di Gregorio, E and Cavalieri, S and Pozzi, E and Mortara, P and Caglio, MM and Balducci, A and Pinessi, L and Langer, T and Padiath, QS and Hakonarson, H and Zhang, X and Brusco, A (2015) An atypical form of AOA2 with myoclonus associated with mutations in SETX and AFG3L2. BMC Medical Genetics, 16 (1).

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Background: Hereditary ataxias are a heterogeneous group of neurodegenerative disorders, where exome sequencing may become an important diagnostic tool to solve clinically or genetically complex cases. Methods: We describe an Italian family in which three sisters were affected by ataxia with postural/intentional myoclonus and involuntary movements at onset, which persisted during the disease. Oculomotor apraxia was absent. Clinical and genetic data did not allow us to exclude autosomal dominant or recessive inheritance and suggest a disease gene. Results: Exome sequencing identified a homozygous c.6292C>T (p.Arg2098*) mutation in SETX and a heterozygous c.346G>A (p.Gly116Arg) mutation in AFG3L2 shared by all three affected individuals. A fourth sister (II.7) had subclinical myoclonic jerks at proximal upper limbs and perioral district, confirmed by electrophysiology, and carried the p.Gly116Arg change. Three siblings were healthy. Conclusions: Exome sequencing is a powerful tool in identifying disease genes. We identified an atypical form of Ataxia with Oculoapraxia type 2 (AOA2) with myoclonus at onset associated with the c.6292C>T (p.Arg2098*) homozygous mutation. Because the same genotype was described in six cases from a Tunisian family with a typical AOA2 without myoclonus, we speculate this latter feature is associated with a second mutated gene, namely AFG3L2 (p.Gly116Arg variant).


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Mancini, C
Orsi, L
Guo, Y
Li, J
Chen, Y
Wang, F
Tian, L
Liu, X
Zhang, J
Jiang, H
Nmezi, BSbcn6@pitt.eduBCN6
Tatsuta, T
Giorgio, E
Di Gregorio, E
Cavalieri, S
Pozzi, E
Mortara, P
Caglio, MM
Balducci, A
Pinessi, L
Langer, T
Padiath, QSqpadiath@pitt.eduQPADIATH
Hakonarson, H
Zhang, X
Brusco, A
Date: 19 March 2015
Date Type: Publication
Journal or Publication Title: BMC Medical Genetics
Volume: 16
Number: 1
DOI or Unique Handle: 10.1186/s12881-015-0159-0
Schools and Programs: School of Public Health > Human Genetics
Refereed: Yes
Date Deposited: 31 Aug 2016 16:10
Last Modified: 30 Mar 2021 13:56


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