Evidence of autosomal dominant Leber congenital amaurosis (LCA) underlain by a CRX heterozygous null allele
- I Perrault1,
- S Hanein1,
- S Gerber1,
- F Barbet1,
- J-L Dufier2,
- A Munnich1,
- J-M Rozet1,
- J Kaplan1
- 1Unité de Recherches sur les Handicaps Génétiques de l’Enfant, Hôpital Necker-Enfants Malades, 149 rue de Sévres, 75743 Paris Cedex 15, France
- 2Service d’Ophtalmologie, Hôpital Necker, France
- Correspondence to: Dr J Kaplan, Unité de Recherches sur les Handicaps Génétiques de l’Enfant, Hôpital Necker-Enfants Malades, 149 rue de Sévres, 75743 Paris Cedex 15, France; kaplan{at}necker.fr
Originally described by Theodore Leber in 1869, Leber congenital amaurosis (LCA, MIM 204000) is the most early and severe form of all hereditary retinal dystrophies, responsible for congenital blindness.1 The diagnosis is usually made at birth or during the first months of life in an infant with total blindness or greatly impaired vision, normal fundus, and unrecordable electroretinogram (ERG).2 It is usually accepted that LCA accounts for 5% of all inherited retinal dystrophies.3 However, this frequency is an underestimate since it is now agreed that in some cases LCA could represent the extreme end of a spectrum of severity of retinal dystrophies.4–6 Hitherto, LCA was considered as an autosomal recessive, genetically heterogeneous condition. Eight LCA genes have been identified or mapped so far, namely (1) the retinal specific guanylate cyclase gene (retGC1) at the LCA1 locus (17p13.1),7 (2) the gene encoding the 65 kDa protein specific to the retinal pigment epithelium (RPE65) at the LCA2 locus (1p31),4,8 (3) the cone-rod homeobox containing gene (CRX, 19q13.3),9–11 (4) the gene encoding the arylhydrocarbon receptor interacting protein-like 1 at the LCA4 locus (17p13.1),12 (5) the gene encoding the retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) at the LCA6 locus (14q11),13,14 (6) the human homologue of the Drosophila melanogaster crumbs gene (CRB1, 1q31),15,16 (7) LCA3 on chromosome 14q24,17 and (8) LCA5 on chromosome 6q.18 The two last loci respectively account for the disease in a consanguineous Saudi Arabian LCA family and a multigenerational kindred of Old Order River Brethren, an isolate originating from Swiss immigrants to America in the 1750s.17,18 Altogether, the six identified genes account for about 48% of LCA cases in our series19 and are consistent with autosomal recessive inheritance. …
