Leber's congenital amaurosis

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Leber's congenital amaurosis
ICD-10 H53.0
ICD-9 362.76
OMIM 204000 204100
DiseasesDB 33192

Leber's congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life

It was first described by Theodore Leber in the 19th century.[1][2] (It should not be confused with Leber's hereditary optic neuropathy, which is a different disease also described by Theodore Leber.)

Presentation

Amaurosis refers to a loss of vision not associated with a lesion, and congenital refers to a condition present from birth (not acquired). However, beyond these general descriptions, the presentation of LCA can vary, because it is associated with multiple genes.

LCA is typically characterized by nystagmus, sluggish or no pupillary responses, and severe vision loss or blindness.

Genetics

It is an autosomal recessive disorder thought to be caused by abnormal development of photoreceptors.

There is evidence tying type 1 LCA to GUCY2D,[3] and type 2 to RPE65.[4]

Other genes which have been implicated include CRB1,[5] CRX, [5] and AIPL1.[6][7]

OMIM currently recognizes 11 types of LCA:[8]

Type OMIM Gene Locus
LCA1 204000 GUCY2D 17p13.1
LCA2 204100 RPE65 1p31
LCA3 604232 RDH12 14q23.3
LCA4 604393 AIPL1 17p13.1
LCA5 604537 LCA5 6q14
LCA6 605446 RPGRIP1 14q11
LCA7 602225 CRX 19q13.3
LCA8 604210 CRB1 1q31-q32.1
LCA9 608553 LCA9 1p36
LCA10 610142 CEP290 12q21.33
LCA11 146690 IMPDH1 7q31.3-q32

The gene CEP290 has been associated with Joubert syndrome, as well as type 10 LCA.[9]

Testing

Project 3000, a foundation started by Chicago Cubs first baseman Derrek Lee and Boston Celtics owner Wyc Grousbeck, works to have the approximately 3,000 people in the United States with the disease genetically tested. [10][11]

Genetic tests and research are currently being performed at the University of Iowa Carver Lab by Drs. Edwin Stone and Val Sheffield.

Treatment

Researchers at Moorfields Eye Hospital in London are conducting the first gene therapy clinical trial for patients with RPE65 LCA.[12] There has been some success in a mouse model with this approach.[13]

References

  1. synd/1189 at Who Named It
  2. T. Leber. Über Retinitis pigmentosa und angeborene Amaurose. Archiv für Ophthalmologie, Berlin, 1869, 15, 3: 1-25.
  3. Perrault I, Rozet JM, Calvas P, et al (1996). "Retinal-specific guanylate cyclase gene mutations in Leber's congenital amaurosis". Nat. Genet. 14 (4): 461–4. doi:10.1038/ng1296-461. PMID 8944027.
  4. Marlhens F, Bareil C, Griffoin JM, et al (1997). "Mutations in RPE65 cause Leber's congenital amaurosis". Nat. Genet. 17 (2): 139–41. doi:10.1038/ng1097-139. PMID 9326927.
  5. 5.0 5.1 Preising MN, Paunescu K, Friedburg C, Lorenz B (2007). "[Genetic and clinical heterogeneity in LCA patients. The end of uniformity]" (in German). Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft 104 (6): 490–8. doi:10.1007/s00347-007-1533-x. PMID 17525851.
  6. Yzer S, Leroy BP, De Baere E, et al (2006). "Microarray-based mutation detection and phenotypic characterization of patients with Leber congenital amaurosis". Invest. Ophthalmol. Vis. Sci. 47 (3): 1167–76. doi:10.1167/iovs.05-0848. PMID 16505055.
  7. BBC NEWS. Retrieved on 2007-09-21.
  8. OMIM - LEBER CONGENITAL AMAUROSIS, TYPE I; LCA1. Retrieved on 2007-09-21.
  9. Traboulsi EI, Koenekoop R, Stone EM (2006). "Lumpers or splitters? The role of molecular diagnosis in Leber congenital amaurosis". Ophthalmic Genet. 27 (4): 113–5. doi:10.1080/13816810601013146. PMID 17148037.
  10. Genetic testing available for Leber's Congenital Amaurosis through Project 3000
  11. USATODAY.com - Cubs' Lee vows to fight daughter's rare disease. Retrieved on 2007-09-21.
  12. BBC NEWS. Retrieved on 2007-09-21.
  13. Pang JJ, Chang B, Kumar A, et al (2006). "Gene therapy restores vision-dependent behavior as well as retinal structure and function in a mouse model of RPE65 Leber congenital amaurosis". Mol. Ther. 13 (3): 565–72. doi:10.1016/j.ymthe.2005.09.001. PMID 16223604.

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