No abstract

No abstract

Recently, Hagerman et al described the occurrence of a late-onset neurological disorder in five male carriers of the fragile-X (FMR-1) premutation. The major characteristics of this disorder, designated the Fragile-X Tremor Ataxia Syndrome (FXTAS), are progressive intention tremor, cerebellar ataxia and cognitive decline. Most cases of FXTAS published thus far were ascertained through families with a known fragile-X proband. Since cerebellar ataxia is one of the main cardinal features, we performed FMR-1 premutation screening in 122 male patients, older than 50 years, who were referred to us for testing of the spinocerebellar ataxia (SCA 1, 2, 3, 6, 7) genes and who were found to be negative. In this group of patients, we found five patients with an FMR-1 premutation. In four of them, a definite diagnosis of FXTAS could be made, based on the proposed diagnostic clinical and radiological criteria for FXTAS. In light of these figures, we recommend that FMR-1 analysis should be included in the molecular diagnostic work-up in the group of male ataxia patients older than 50 years. The presence of symmetrical regions of increased T2 signal intensity in the middle cerebellar peduncles (MCP) and adjacent white matter is thought to be a specific sign and included as radiological inclusion criterion for this syndrome. Data of a large survey have demonstrated an agerelated penetrance of the combination of reported tremor and ataxia in male premutation carriers, going up to 47% in the group of 70 -79 years. 3Most cases of FXTAS published thus far were ascertained through families with a known fragile-X proband. Since cerebellar ataxia is one of the main cardinal features, we decided to perform fragile X premutation screening in male patients, who were referred to our laboratory for testing of the spinocerebellar ataxia (SCA) genes and who were found to be negative for the expansion. We retrospectively selected all male probands with ataxia, who were 50 years or older at the time of referral. Of 137 patients, 15 (10.9%) were found positive for an (CAG)n expansion in one of the SCA genes. Of the remaining 122 men, all were

No abstract

The cytogenetic and DNA constitution of the foetus indicated the isochromosome 12p to be of paternal origin, and implied post-zygotic formation of the isochromosome 12p in the Pallister-Killian syndrome.