Infantile and childhood retinal blindness

A molecular perspective (The Franceschetti Lecture)

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Much progress has been made in the past five years in the understanding of Leber congenital amaurosis (LCA) and allied early-onset retinal dystrophies, various forms of stationary sensory retinal blindness, and genes that are involved in the development of the retina. Uncomplicated Leber congenital amaurosis has been associated with mutations of six genes: GUCY2D (encoding RetGC-1) at 17p13.1, RPE65 at 1q31, CRX at 19q13.3, AIPLI at 17p13.1, CRB1 at 1q31-3, and RPGRIP at 14q11. A similar early-onset severe retinal degeneration phenotype has been associated with mutation of TULP1 at 6p21.3. Leber appreciated that the condition he described merged with the phenotypes of early childhood-onset severe retinal degenerations. This insight has been confirmed at the molecular level for mutations of GUCY2D, RPE65, CRX, AIPL1, and CRB1, which cause not only LCA, but also early-childhood and even adult-onset retinal degenerations. This paper reviews the new finding of LCA from mutations of CRB1 and discusses the molecular basis of X-linked blue monochromacy, autosomal recessive congenital achromatopsia from mutations of the genes for ACHM2 (CNGA3) and ACHM3 (CNGB3), X-linked congenital stationary night blindness (CSNB) from mutations of CACNA1F (incomplete CSNB) and NYX (complete CSNB), and the enhanced S-cone syndrome from mutation of the developmental gene, NR2E3 at 15q23, which appears to regulate the development of M- and L-cones from S-cones. These discoveries have opened new areas of cellular and developmental biology for future research into the causes of retinal blindness.

Original languageEnglish (US)
Pages (from-to)71-97
Number of pages27
JournalOphthalmic Genetics
Volume23
Issue number2
DOIs
StatePublished - 2002

Fingerprint

Blindness
Leber Congenital Amaurosis
Mutation
Retinal Degeneration
Retinal Dystrophies
Color Vision Defects
Genes
Developmental Genes
Phenotype
Developmental Biology
Cell Biology
Retina
Congenital stationary night blindness

Keywords

  • Achromatopsia
  • Congenital stationary night blindness
  • Enhanced S-cone syndrome
  • Franceschetti Lecture
  • Leber amaurosis
  • Molecular
  • Retinal blindness
  • Review

ASJC Scopus subject areas

  • Ophthalmology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)

Cite this

Infantile and childhood retinal blindness : A molecular perspective (The Franceschetti Lecture). / Weleber, Richard.

In: Ophthalmic Genetics, Vol. 23, No. 2, 2002, p. 71-97.

Research output: Contribution to journalArticle

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