Complete deletion of the aprataxin gene: ataxia with oculomotor apraxia type 1 with severe phenotype and cognitive deficit

Abstract

Ataxia with oculomotor apraxia type 1 (AOA1) is a recently described autosomal-recessive neurodegenerative condition of childhood onset. It is caused by mutations in the APTX gene, which encodes the protein aprataxin. Clinical features include gait and limb ataxia, dysarthria, oculomotor apraxia, mild peripheral neuropathy and progression of neurological deficits.1 Some patients manifest parkinsonian symptoms or mental retardation, although the latter has been reported predominantly in Japanese patients.2 We report a patient with homozygous deletion of APTX, who presented with behavioural changes (social withdrawal), and subsequent rapid progression of neurological symptoms associated with severe cognitive decline. We suggest that complete deletion of APTX is associated with a more severe phenotype than that associated with point mutations.

DNA damage to human genetic disorders with neurodevelopmental defects

“…The most common mutation is the insertion of a T after nucleotide 167 and the p.Pro206Leu mutation [69]. AOA1 patients with complete deletion of the APTX gene were also found [72,73].…”

Novel APTX Mutation in a Hispanic Subject Affected by Ataxia with Oculomotor Apraxia Type 1

“…AOA1 cases have been described in France, Italy, and Tunisia . Recent reports indicate that AOA1 is present in a wide range of ethnic populations . However, AOA1 has not been described among Hispanic subjects.…”

“…The phenotype is classical for this condition, except for the lack of OMA, which is observed in up to 86% of cases . Genotype‐phenotype correlations in AOA1 can be made to some degree, but some reports yielded contradicting results . Even though the aprataxin protein is involved in DNA repair, there is no evidence indicating cancer predisposition in AOA1 .…”

Identification of APTX disease-causing mutation in two unrelated Jordanian families with cerebellar ataxia and sensitivity to DNA damaging agents

“…More than 40 different APTX mutations have been identified so far, including nonsense, missense, splice site, frameshift mutations, as well as a complete deletion of the APTX gene [2,3,[8][9][10][11][12]. The most common form of ARCAs in Japan and Portugal is AOA1, with the c.689_690insT (p.Glu232fs) mutation being the most frequent one observed in Japan, while the c.837G>A (p.Trp279X) was the most common mutation among the Portuguese patients [9,13].…”