|
|
|
| August 2000, Volume 8, Number 8, Pages 649-651 |
| Table of contents Previous Abstract Next Article PDF |
 |
| Short Report |
| Identification of genetic heterogeneity in Refsum's disease |
|
| Anthony S Wierzbicki1,2, John Mitchell3, Michelle Lambert-Hammill1, Margaret Hancock2, Juliet Greenwood3, Margaret C Sidey4, Jacqueline de Belleroche3 and F Brian Gibberd4 |
|
1Department of Chemical Pathology, King's Guy's & St Thomas' Medical School, King' College, London, UK
2Department of Chemical Pathology, Imperial College of Science, Technology and Medicine, Chelsea & Westminster Hospital, London, UK
3Department of Neuromuscular Disease, Imperial College of Science, Technology and Medicine, Charing Cross Hospital, London, UK
4Department of Clinical Pharmacology and Therapeutics, Imperial College of Science, Technology and Medicine, Chelsea & Westminster Hospital, London, UK
|
|
Correspondence to: DrA S Wierzbicki , Department of Chemical Pathology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK. Tel: +44 20 7 928 9292 x 2027; Fax: +44 20 7 928 4226; E-mail: Anthony.Wierzbicki@kcl.ac.uk
|
|
| Abstract |
| Refsum's disease (MIM 266500) is a recessive disorder characterised by defective peroxisomal alpha-oxidation of phytanic acid. A Refsum's disease gene, phytanoyl-CoA hydroxylase (PAHX), has been localised to chromosome 10p13 between the markers D10S226-D10S223. This study investigated whether all cases of Refsum's disease were linked with chromosome 10p13. Eight genetically informative families comprising 92 individuals including 17 living patients with a Refsum's disease phenotype and initial plasma phytanic acid >200  mol/L were recruited. Linkage to the 10pter-10p11.2 region was investigated using a panel of eight dinucleotide repeat markers. Linkage analysis of this phenotypically identical cohort suggested that Refsum's disease was genetically heterogeneous (Zmax = 5.28,  = 0.45). Two subgroups were identified. One group of four families with eight affected individuals had a maximum multipoint lod score for linkage of 3.89 in the region D10S547 to D10S191, whilst in another three families with nine affected individuals linkage to this region was definitely excluded. Our results show that Refsum's disease is genetically heterogeneous, with up to 55% of cases not being linked to the PAHX gene locus at D10S547 to D10S223. This suggests that Refsum's disease, in common with other peroxisomal 'diseases', may be more accurately described as a heterogeneous syndrome. European Journal of Human Genetics (2000) 8, 649-651. |
|
| Keywords |
| Refsum's disease; phytanic acid; linkage; heterogeneity |
|
|
|
|
| Received 5 July 1999; revised 6 April 2000; accepted 27 April 2000 |
|
| August 2000, Volume 8, Number 8, Pages 649-651 |
| Table of contents Previous Abstract Next Article PDF |
|
|
