J Med Genet 1999;36:447-451 ( June )

Mutations of the retinal specific ATP binding transporter gene (ABCR) in a single family segregating both autosomal recessive retinitis pigmentosa RP19 and Stargardt disease: evidence of clinical heterogeneity at this locus

Jean-Michet Rozet^a, Sylvie Gerber^a, Imad Ghazi^b, Isabelle Perrault^a, Dominique Ducroq^a, Eric Souied^a, Annick Cabot^a, Jean-Louis Dufier^b, Arnold Munnich^a, Josseline Kaplan^a

^a Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U-393 and Département de Génétique, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France, ^b Service d'Ophtalmologie, Hôpital Laënnec, Paris, France

Correspondence to: Dr Kaplan.

Received 23 November 1998; Revised version accepted for publication 1 March 1999

Stargardt disease (STGD) is an autosomal recessive macular dystrophy of childhood characterised by bilateral loss of central vision over a period of several months. STGD has been mapped to chromosome 1p22.1 and recently ascribed to mutations in the retinal specific ATP binding transporter gene (ABCR). The fundus flavimaculatus with macular dystrophy (FFM), an autosomal recessive condition responsible for gradual loss of visual acuity in adulthood (second to third decade) has also been mapped to the same locus. However, a gene for autosomal recessive retinitis pigmentosa with distinctive features of choriocapillaris atrophy at an advanced stage (RP19) has been mapped to the genetic interval encompassing the STGD gene on chromosome 1p (D1S435-D1S236), raising the question of whether, despite striking differences in clinical course and presentation, RP19 and STGD might be allelic disorders at the ABCR locus.
In a family segregating RP and STGD in two first cousins, we found that heterozygosity for a splicing mutation in the ABCR gene (1938-1 GA) resulted in STGD while hemizygosity for this splice mutation resulted in RP, and when studying the RP patient's parents, we found a maternal non-contribution with apparent segregation of a null allele ascribed to a partial deletion of the ABCR gene.
The present study shows that, despite striking clinical differences, RP19 and STGD are allelic disorders at the ABCR locus.


Keywords: Stargardt disease; RP19; ABCR gene

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© 1999 by J Med Genet
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