Objective: To describe a consanguineous family with ataxia with oculomotor apraxia, type II (AOA2).

Background: AOA2 is an autosomal recessive neurodegenerative syndrome leading to progressive cerebellar ataxia with apraxia of eye movements, peripheral neuropathy, cerebellar atrophy and elevated alpha-feto-protein (AFP) caused by mutations in the senataxin (SETX) gene. Here we report the clinical and genetic characteristics of a consanguinous family with 2 mutations in the SETX gene.

Methods: The proband and seven family members underwent a medical history, neurological examination, and an International Cooperative Ataxia Rating Scale (ICARS) was performed. Saliva and blood were collected, and DNA and RNA were extracted for genetic studies. SETX mutations were evaluated by Sanger sequencing and SETX mRNA was evaluated by quantitative RT-PCR.

Results: The proband, five of his siblings, and their mother were investigated. In addition to the AOA2-manifesting proband, one sibling was clinically affected with cerebellar ataxia, oculomotor apraxia and neuropathy, while the mother and four siblings were neurologically normal. Both clinically affected members of the family had tandem mutations in SETX (c.6292C>T ; p.Arg2098X and c.1274G>C ; p.Gly425Ala) on both alleles, while two unaffected siblings were heterozygous for both mutations. Surprisingly, mRNA transcript levels were variably affected by these mutations.

Conclusions: Autosomal recessive, loss of function mutations in the SETX gene are associated with the clinical syndrome of AOA2. Here we describe a family carrying two mutations in the SETX gene. Two siblings that are homozygous for both mutations demonstrate classic symptoms of AOA2, while two heterozygous carriers are unaffected. mRNA transcript levels of SETX were not clearly correlated with mutation status.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-molecular-characterization-of-a-family-with-ataxia-with-oculomotor-apraxia-type-2/