Ataxia-ocular motor apraxia syndrome: an investigation of cellular radiosensitivity of patients and their families.

Abstract

Although ataxia-ocular motor apraxia (AOA) has been described as a disease entity mimicking ataxia telangiectasia (AT), no radiobiological studies have been carried out on cells from patients with AOA to find their possible relationship to AT. In the present study, cultured fibroblasts from three patients with AOA and their asymptomatic relatives (parents and sibs) were, therefore, compared with those from a classical AT homozygote, an AT heterozygote, and four healthy subjects for cell survival after acute and chronic irradiation. While a moderately increased cellular sensitivity (compared to normal) was observed in two AOA patients and most of their relatives, the degree of their radiosensitivity was quite different from that ofthe AT homozygote after both acute and chronic irradiation. One AOA patient exhibited increased cellular sensitivity similar to that of a classical AT homozygote up to 4% survival level after chronic irradiation but not after acute irradiation. A comparison of peripheral blood lymphocytes from two AOA patients, an AT homozygote, and two normal controls for spontaneous and (acute) radiation induced chromosomal breaks also failed to show any similarity between AOA and AT. These data support the notion that AOA is different from classical AT, and may represent a distinct disease entity controlled by specific gene(s), or compound heterozygotes involving different AT genes promoting the manifestation of AOA characteristics. (JMed Genet 1994;31:953-956)

Autosomal Recessive Cerebellar Ataxia with Oculomotor Apraxia (Ataxia-Telangiectasia–Like Syndrome) Is Linked to Chromosome 9q34

“…In summary, we have identified a novel locus for a primary autosomal recessive cerebellar ataxia whose features resemble those of AT. The clinical features in the family we studied are very similar to those of other patients with AOA described in the literature (Aicardi et al 1988;Hannan et al 1994;Gascon et al 1995). However, it is not yet clear whether AOA is genetically homogeneous; this will require the analysis of additional families.…”

“…Results of computed tomography (CT) were normal in six patients and revealed mild cerebellar vermis atrophy in three. Three additional patients, from two consanguineous families, were reported with AOA that presented in early childhood (Hannan et al 1994;Gascon et al 1995). Again, detailed investigations of sensitivity to acute and chronic ionizing radiation did not reveal abnormalities typical of AT.…”

“…Again, detailed investigations of sensitivity to acute and chronic ionizing radiation did not reveal abnormalities typical of AT. On the basis of lack of laboratory evidence for chromosomal instability, it was suggested that AOA was a neurological and genetic entity separate from AT (Aicardi et al 1988;Hannan et al 1994;Gascon et al 1995). However, the families reported were too small to permit linkage analysis, and there has been little progress in determining the genetic basis of AOA/ATL.…”