Analysis of the monoamine oxidase genes and the Norrie disease gene locus in narcolepsy

It seems fairly clear that patients’ recall of statistical data related to risk is limited, even in the short term, and informed consent based on verbal information alone is not enough, and that an information letter should be given to each patient as a part of the process of informed consent.

Abstract

Narcolepsy is linked to both HLA class II and non-HLA genes. Most cases are of unknown cause, but abnormal REM sleep symptoms suggestive of narcolepsy have been described in association with Norrie disease. 1 Vossler DG Wyler AR Wilkus RJ et al. Cataplexy and monoamine oxidase deficiency in Norrie disease. Neurology. 1996; 46: 1258-1261 Crossref PubMed Google Scholar This is an X-linked recessive disorder causing ocular atrophy. Monoamine oxidase (MAO) genetic and biochemical defects occur in some of these subjects and the gene for Norrie disease is in close proximity (within 100 kb) to both MAO A and B coding sequences. 2 Chen ZY Denney RM Breakfield XO Norrie disease and MAO genes: nearest neighbours. Hum Mol Genet. 1995; 4: 1729-1737 Crossref PubMed Scopus (66) Google Scholar We report on the Norrie disease gene area in narcolepsy. We studied markers embracing the Norrie disease chromosomal area in Xp11.3/p11.4 (tel-MAOA-MAOB-ND-cen) in 28 subjects with definite narcolepsy, all with cataplexy (16 male, 12 female, 27 white, 1 black, 20 HLA DR2 positive, 8 DR2 negative) and 49 (DR2 positive control patients with normal sleep-wake habits (33 male, 16 female, all white). No patient had Norrie disease. We looked for microdeletions in the Norrie disease coding region by polymerase chain reactions using primer sets for exons one, two, and three. 3 Berger W Meindl A van de Pol TJ et al. Isolation of a candidate gene for Norrie's disease by positional cloning. Nat Genet. 1992; 1: 199-203 Crossref PubMed Scopus (199) Google Scholar We also genotyped for a series of microsatellite markers covering the 5′ regions of MAOA and MAOB genes. These should identify both intragenic and promoter-region mutations. For MAOA these were the dinucleotide repeat markers from intron 2 and a variable number tandem repeat (VNTR) marker from intron 1; for MAOB, a dinucleotide repeat in intron 2, and novel repeats in introns 1 and 3, a novel VNTR in intron 3, and a novel dinucleotide repeat 22 kb 5′ to the first exon.