Preferred Label : Leber congenital amaurosis 1;
Symbol : LCA1;
CISMeF acronym : CRB; LCA; LCA1;
Type : Phenotype, molecular basis known;
Alternative titles and symbols : Amaurosis congenita of leber I; CRB; Retinal blindness, congenital; LCA;
Description : Leber congenital amaurosis comprises a group of early-onset childhood retinal dystrophies
characterized by vision loss, nystagmus, and severe retinal dysfunction. Patients
usually present at birth with profound vision loss and pendular nystagmus. Electroretinogram
(ERG) responses are usually nonrecordable. Other clinical findings may include high
hypermetropia, photodysphoria, oculodigital sign, keratoconus, cataracts, and a variable
appearance to the fundus (summary by Chung and Traboulsi, 2009). - Genetic Heterogeneity
of Leber Congenital Amaurosis LCA2 (204100) is caused by mutation in the RPE65 gene
(RPE65; 180069) on chromosome 1p31. LCA3 (604232) is caused by mutation in the SPATA7
gene (609868) on chromosome 14q31.3. LCA4 (604393) is caused by mutation in the AIPL1
gene (604392) on chromosome 17p13.1. LCA5 (604537) is caused by mutation in the LCA5
gene (611408) on chromosome 6q14.1. LCA6 (613826) is caused by mutation in the RPGRIP1
gene (605446) on chromosome 14q11. LCA7 (613829) is caused by mutation in the CRX
gene (602225) on chromosome 19q13.3. LCA8 (613835) is caused by mutation in the CRB1
gene (604210) on chromosome 1q31-q32. LCA9 (608553) is a locus that has been mapped
to chromosome 1p36. LCA10 (611755) is caused by mutation in the CEP290 gene (610142)
on chromosome 12q21 and may account for as many as 21% of cases of LCA. LCA11 (613837)
is caused by mutation in the IMPDH1 gene (146690) on chromosome 7q31.3-q32. LCA12
(610612) is caused by mutation in the RD3 gene (180040) on chromosome 1q32.3. LCA13
(612712) is caused by mutation in the RDH12 gene (608830) on chromosome 14q24.1. LCA14
(613341) is caused by mutation in the LRAT gene (604863) on chromosome 4q31. LCA15
(613843) is caused by mutation in the TULP1 gene (602280) on chromosome 6p21.3. LCA16
(614186) is caused by mutation in the KCNJ13 gene (603208) on chromosome 2q37. Perrault
et al. (1999) provided a review of Leber congenital amaurosis, with emphasis on genetic
heterogeneity. Wiszniewski et al. (2011) analyzed 13 known LCA genes in 60 LCA probands,
and identified homozygous or compound heterozygous mutations in 42 (70%). In addition,
a third disease-associated mutant allele at a second locus was identified in 7 (12%)
of the 60 patients. Wiszniewski et al. (2011) stated that the significance of the
third mutated allele was unknown, but suggested that mutational load might be important
to penetrance of the LCA phenotype. Because LCA manifests very early in life and results
in profound vision loss, patients with mutations in other syndromic or nonsyndromic
eye disease genes may receive an initial diagnosis of LCA, prior to development of
syndromic features or before more thorough phenotyping can be performed (see, e.g.,
Senior-Loken syndrome-5, 609254).;
Inheritance : Autosomal recessive;
Molecular basis : Caused by mutation in the guanylate cyclase 2D, membrane, retina-specific gene (GUCY2D,
600179.0001);
Laboratory abnormalities : Hyperthreoninemia; Hyperthreoninuria;
Prefixed ID : #204000;
Origin ID : 204000;
UMLS CUI : C2931258;
Automatic exact mappings (from CISMeF team)
- Broader ORDO disease(s)
- Currated CISMeF NLP mapping
- DO Cross reference
- False automatic mappings
- Genes related to phenotype
- HPO term(s)
- ORDO concept(s)
- Semantic type(s)
- UMLS correspondences (same concept)
