Giroux and Barbeau previously described a unique French-Canadian family segregating a combination of ataxia and hyperkeratotic erythematous plaques in an autosomal dominant mode. These skin lesions were compatible with erythrokeratodermia (EK). The family has been partially collected and the disease was potentially linked to chromosome 1p35. However, the identification of the mutated gene is pending. The objective of this study is to revisit the clinical phenotype and genetic mapping of this peculiar family. We recently reassessed the family with detailed examinations, brain MRI and EMG studies.We recollected the family and performed a whole genome scan analysis by using microsatellites markers. We also analyzed four additional families from European ancestry with autosomal dominant SCA (from the EuroSCA consortium), for which a genome scan have shown positive LOD score to the same chromosomal region. The neurological phenotype in the French-Canadian family is compatible with a pure autosomal dominant cerebellar ataxia (ADCA type III in Harding’s classification) associated with cerebellar atrophy starting in late 40s. We mapped the locus for the disease on chromosome 6p12.3-q16.1 with a maximum LOD score of 5.33 for marker D6S452. Haplotype analysis of this family allowed us to refine the candidate gene region between markers D6S459 and D6S417 (46.8Mb). Linkage to this locus was confirmed in the four additional families with a maximum compiled LOD score of 9.9. So far, the sequencing of 17 candidate genes, search for CAG/CTG expansion and copy number analysis did not allow the identification of the causative gene. We have mapped a new locus for a pure autosomal dominant cerebellar ataxia (SCA31) in a total of five families from European ancestry, including a large French-Canadian family associated with EK.

A new locus for pure Spinocerebellar Ataxia associated with Erythrokeratodermia maps to chromosome 6p12.3-q16.1

DI GREGORIO, ELEONORA;BRUSCO, Alfredo;
2009

Abstract

Giroux and Barbeau previously described a unique French-Canadian family segregating a combination of ataxia and hyperkeratotic erythematous plaques in an autosomal dominant mode. These skin lesions were compatible with erythrokeratodermia (EK). The family has been partially collected and the disease was potentially linked to chromosome 1p35. However, the identification of the mutated gene is pending. The objective of this study is to revisit the clinical phenotype and genetic mapping of this peculiar family. We recently reassessed the family with detailed examinations, brain MRI and EMG studies.We recollected the family and performed a whole genome scan analysis by using microsatellites markers. We also analyzed four additional families from European ancestry with autosomal dominant SCA (from the EuroSCA consortium), for which a genome scan have shown positive LOD score to the same chromosomal region. The neurological phenotype in the French-Canadian family is compatible with a pure autosomal dominant cerebellar ataxia (ADCA type III in Harding’s classification) associated with cerebellar atrophy starting in late 40s. We mapped the locus for the disease on chromosome 6p12.3-q16.1 with a maximum LOD score of 5.33 for marker D6S452. Haplotype analysis of this family allowed us to refine the candidate gene region between markers D6S459 and D6S417 (46.8Mb). Linkage to this locus was confirmed in the four additional families with a maximum compiled LOD score of 9.9. So far, the sequencing of 17 candidate genes, search for CAG/CTG expansion and copy number analysis did not allow the identification of the causative gene. We have mapped a new locus for a pure autosomal dominant cerebellar ataxia (SCA31) in a total of five families from European ancestry, including a large French-Canadian family associated with EK.
59th Annual meeting of the American Society of Human Genetics
Honolulu, Hawai
October 20-24, 2009
59th Annual meeting of the American Society of Human Genetics
The American Society of Human Genetics
-
158
158
SCA15; ITPR1; ataxia
M. Turcotte Gauthier; D.K. Nguyen; C. Meloche; J. Poirier; S.L. Girard; S. Forlani; E. Di Gregorio; B. Borroni; G. De Michele; A. Filla; D. Verbeek; B.P.C. Van de Warrenburg; C.A. Drouin; A. Durr; A. Brice; G. Stevanin; A. Brusco; P. Cossette1
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/133684
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