Investigation of Recessive Ataxia Loci in Patients with Young Age of Onset

Abstract

Autosomal recessive cerebellar ataxias are a phenotypically and genetically heterogeneous group of diseases. Major forms can be distinguished on the basis of clinical signs, age of onset, biochemical parameters or genotypes. To develop rational diagnostic strategies, phenotypic information, e.g., age of onset combined with population-specific disease frequencies could be highly favourable. We tested this hypothesis for single candidate loci and mutations in North European ataxia patients with juvenile and early adult onset. While we could prove that Friedreich ataxia (FRDA) is frequent in Germany, only few patients with ataxia-oculomotor apraxia type 1 (AOA1) and type 2 (AOA2) were diagnosed. The frequency of the mitochondrial recessive ataxia syndrome (MIRAS) and the infantile onset spinocerebellar ataxia (IOSCA) in this population remains unknown since no case with the common mutation of the corresponding gene was detected.

Sensorimotor neuronopathy in ataxia with oculomotor apraxia type 2

“…14 The SETX gene has an open reading frame of 8031 nucleotides and 24 exons. 27 AOA2 has been associated with homozygous 3,4,6,11,12,19,21,23,31 and compound heterozygous 1,12,13,21,31 alterations that cause frameshift, nonsense, and missense mutations, and a restricted form of the disease resulted from two in cis-dominant SETX gene mutations. 5 Missense mutations in the SETX gene that cause ALS 4 cannot be distinguished at present from those that cause AOA2.…”

Low predisposition to instability of the Friedreich ataxia gene in Cuban population

“…The prevalence of FRDA varies widely from one ethnic group to another, being low in Norway (7), Finland (8), and Mexico (9), and rare in the Far East, sub‐Saharan Africa, and among the Native Americans (10, 11). Meanwhile, it is the most commonly inherited ataxia among Caucasians, having a high frequency in Germany (12), Cyprus (13), and being responsible for 64% of recessively inherited ataxias in Brazilian and Portuguese families (14).…”

Ataxias with Autosomal, X-Chromosomal or Maternal Inheritance

“…Oculography may reveal impaired smooth pursuit, defective saccade accuracy, hyperreflexive vestibulo-ocular reflexes 92 . As the causative mutation a CAG/CAA expansion of 46-63 repeats in the TATA-box binding protein has been identified ( Table 3) 16,93,95 . SCA17 is unique in that the poly-Q tract is encoded by either long stretches of pure CAGs or a complex configuration containing CAA interruptions 91 .…”