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Early onset, non-progressive, mild cerebellar ataxia co-segregating with a familial balanced translocation t(8;20)(p22;q13)
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  1. J M Hertz1,
  2. B Sivertsen2,
  3. A Silahtaroglu3,
  4. M Bugge3,
  5. V Kalscheuer4,
  6. A Weber4,5,
  7. J Wirth4,6,
  8. H-H Ropers4,
  9. N Tommerup3,
  10. Z Tümer3
  1. 1Department of Clinical Genetics, Aarhus University Hospital, DK-8000 Aarhus C, Denmark
  2. 2Department of Neurology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark
  3. 3Wilhelm Johannsen Centre for Functional Genome Research, Department of Medical Genetics, IMBG, The Panum Institute, University of Copenhagen, Denmark
  4. 4Max-Planck Institute of Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany
  5. 5Institute of Neuroimmunology, Neuroscience Research Center, Charité University Hospital, D-10098 Berlin, Germany
  6. 6Developmental Biology and Molecular Pathology, University of Bielefeld, Bielefeld, Germany
  1. Correspondence to:
 Dr J M Hertz
 Department of Clinical Genetics, Aarhus University Hospital, The Bartholin Building, DK-8000 Aarhus C, Denmark; hertzakh.aaa.dk

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Hereditary ataxia is a clinically and genetically heterogenous group of disorders. Most are progressive and associated with other neurological abnormalities. Early onset, non-progressive cerebellar ataxia (OMIM #117360) has been described as a dominantly inherited disorder associated with isolated vermal atrophy1–3 or generalised atrophy of the cerebellum.4,5 This is a rare entity compared with autosomal recessive early onset cerebellar ataxia with retained tendon reflexes (OMIM #212895).6

Various disease genes have been identified using rare disease associated balanced chromosomal rearrangements (DBCRs), for example, translocations or inversions that truncate, delete, or otherwise inactivate genes.7 DBCRs may occur in at least 1% of patients with autosomal dominant disorders caused by haploinsufficiency, and in many girls affected by X linked recessive disorders. During a systematic search for apparently balanced chromosomal rearrangements associated with abnormal phenotypes,7 we identified a four generation family in which a variable neurological phenotype including an early onset, non-progressive, and mild cerebellar ataxia segregates together with a balanced reciprocal translocation.

MATERIALS AND METHODS

Family history

The study was approved by the local ethics committee (no. 1992–2489). The family consists of four generations as shown in fig 1. All family members, except II:2, were personally interviewed and underwent neurological examination by one of us (BS). The affected members in generations III, IV, and V have developed a phenotype of clumsiness starting in early childhood (1–7 years), including gait abnormalities with lurching and frequent falling, which increased upon physical activity. Objective findings included ataxia, dysmetria on finger to nose and/or heel to shin test, tremor, nystagmus, and retained reflexes in the lower limbs. Neurological symptoms and the phenotype of the affected members are presented in table 1. MRI of two of the patients (III:2 and III:4) performed at 49 and 43 years of age, respectively, gave inconclusive results. Anticipation was not observed …

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