Homozygosity mapping of Portuguese and Japanese forms of ataxia-oculomotor apraxia to 9p13, and evidence for genetic heterogeneity.

• Autor(a) principal: Moreira, M.C.
• Data de Publicação: 2001
• Outros Autores: Barbot, C., Tachi, N., Kozuka, N., Mendonça, P., Barros, J., Coutinho, P., Sequeiros, J., Koenig, M.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.16/503

Am J Hum Genet. 2001 Feb;68(2):501-8. Epub 2001 Jan 22. Homozygosity mapping of Portuguese and Japanese forms of ataxia-oculomotor apraxia to 9p13, and evidence for genetic heterogeneity. Moreira MC, Barbot C, Tachi N, Kozuka N, Mendonça P, Barros J, Coutinho P, Sequeiros J, Koenig M. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis-Pasteur, Illkirch, C.U. de Strasbourg, France. Abstract Ataxia with oculomotor apraxia (AOA) is characterized by early-onset cerebellar ataxia, ocular apraxia, early areflexia, late peripheral neuropathy, slow progression, severe motor handicap, and absence of both telangiectasias and immunodeficiency. We studied 13 Portuguese families with AOA and found that the two largest families show linkage to 9p, with LOD scores of 4.13 and 3.82, respectively, at a recombination fraction of 0. These and three smaller families, all from northern Portugal, showed homozygosity and haplotype sharing over a 2-cM region on 9p13, demonstrating the existence of both a founding event and linkage to this locus, AOA1, in the five families. Three other families were excluded from this locus, demonstrating nonallelic heterogeneity in AOA. Early-onset cerebellar ataxia with hypoalbuminemia (EOCA-HA), so far described only in Japan, is characterized by marked cerebellar atrophy, peripheral neuropathy, mental retardation, and, occasionally, oculomotor apraxia. Two unrelated Japanese families with EOCA-HA were analyzed and appeared to show linkage to the AOA1 locus. Subsequently, hypoalbuminemia was found in all five Portuguese patients with AOA1 with a long disease duration, suggesting that AOA1 and EOCA-HA correspond to the same entity that accounts for a significant proportion of all recessive ataxias. The narrow localization of AOA1 should prompt the identification of the defective gene. PMID: 11170899 [PubMed - indexed for MEDLINE]PMCID: PMC1235299Free PMC Article Images from this publication.See all images (3) Free text Figure 1Simplified pedigrees of the families with AOA that show linkage to 9p13, and of family AOAP9. Markers are shown, from top to bottom, in their pter-qter order (from GeneMap'99). Haplotypes linked to the disease are boxed, and homozygosity in patients is shaded in gray. Distance (cM) to the previous m...Homozygosity Mapping of Portuguese and Japanese Forms of Ataxia-Oculomotor Apraxia to 9p13, and Evidence for Genetic HeterogeneityAm J Hum Genet. 2001 February;68(2):501-508.Figure 2Haplotypes in families AOAP1, -P4, -P5, -P7, -P11, and -P9 and in AOAJ1 and -J2. Homozygous alleles are indicated only once per family. Alleles homozygous by descent are in boldface. The shared haplotypes are boxed and shaded in gray. Alleles that might belong to the founding haplotypes are boxed wi...Homozygosity Mapping of Portuguese and Japanese Forms of Ataxia-Oculomotor Apraxia to 9p13, and Evidence for Genetic HeterogeneityAm J Hum Genet. 2001 February;68(2):501-508.Figure 3Geographical distribution, on the Portuguese mainland, of families with AOA. Districts where the survey is already completed are shaded in gray. Family AOAP13 is not represented, because of its African (Cabo Verde) origin. The three families in the Braga region that show linkage to 9p are AOAP4, -P7...Homozygosity Mapping of Portuguese and Japanese Forms of Ataxia-Oculomotor Apraxia to 9p13, and Evidence for Genetic HeterogeneityAm J Hum Genet. 2001 February;68(2):501-508.