Leber Congenital Amaurosis 8

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

RPGRIP1, CRX, CRB1, NMNAT1, RPE65, AIPL1, CEP290, IQCB1, LCA5, SPATA7, TULP1, KCNJ13, LRAT, IMPDH1, RD3, GUCY2D, RDH12, USP45, GDF6, MERTK, IFT140, PCYT1A, MPP5, ABCA4, CLUAP1, USH2A, SLC38A8, CDHR1, GRM6, RP2, AHI1, PDE6A, CNGB3, GIGYF2, ZFYVE26, NR2E3, RGS9, CRB2, LCA10, OTX2, CLTA, PTPRC, MYO7A, CNGA3, CCT2, GUCA1A, PRPH2, IMPG1, CABP4, GUCY2F, SLC7A14, GUCA1B, LPCAT1, HSD17B6, ENO2, CNTLN, PSMD13, PRPH, GUCY2EP, BCL2, MIR204, EGF, SP4, RPGR, NUB1, ADH7, NRL, TUB, ND4, FST, SLC19A2, PRPF8, PNPLA6, CILK1, NINL, SERPINF1, RPGRIP1L, MEF2C, TAP2, MEF2A, ELOVL4, IMPG2, PDE6B

Drugs

9-cis-Retinyl acetate, Adeno-associated viral vector serotype 8 containing the human AIPL1 gene, Adeno-associated viral vector serotype 8 containing the human GUCY2D gene

9-cis-Retinyl acetate, Adeno-associated viral vector serotype 8 containing the human AIPL1 gene, Adeno-associated viral vector serotype 8 containing the human GUCY2D gene, Adeno-associated virus serotype 8 containing the human RdCVF sequence and the human RdCVFL sequence, Adenovirus associated viral vector serotype 4 containing the human RPE65 gene, Adenovirus associated viral vector serotype 5 containing the human RPE65 gene, Adenovirus-associated viral vector serotype 2 containing the human RPE65 gene (AAV2-hRPE65v2 ), Antisense oligonucleotide complementary to the exonic splicer enhancer sequence at intron 26 of the centrosomal protein 290 pre-mRNA, Combination of three adeno-associated viral vectors of serotype 8 containing the 5'-, the body- and the 3'- coding sequences of human CEP290 fused to inteins, Recombinant adeno-associated viral vector serotype 5 encoding Staphylococcus aureus Cas9 endonuclease and two guide RNAs complementary to two regions of intron 26 of the CEP290 gene

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A number sign (#) is used with this entry because Leber congenital amaurosis-8 (LCA8) is caused by homozygous or compound heterozygous mutation in the CRB1 gene (604210) on chromosome 1q31.

Homozygous or compound heterozygous mutation in CRB1 can also cause retinitis pigmentosa-12 (RP12; 600105).

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).

For a general description and a discussion of genetic heterogeneity of LCA, see 204000.

Clinical Features

Abouzeid et al. (2006) reported 4 members of a Middle Eastern family with Leber congenital amaurosis who had high to extreme hyperopia (average spherical refractive errors ranging from +5.00 to +10.00).

Molecular Genetics

Lotery et al. (2001) screened the candidate gene CRB1 in 190 patients with Leber congenital amaurosis (LCA8; 613835) who were negative for mutation in 6 known LCA genes and 140 controls, and identified 21 patients and 2 controls who harbored amino acid-altering sequence variants (p = 0.03; see, e.g., 604210.0013). The authors noted that the 21 CRB1 mutation-carrying patients represented 9% of their total cohort of 233 LCA patients, making CRB1 the most commonly mutated gene in this group of patients.

Den Hollander et al. (2001) identified mutations in the CRB1 gene in 7 of 52 patients with LCA from the Netherlands, Germany, and the US. In 2 affected brothers, they identified compound heterozygous mutations (604210.0006-604210.0007). Den Hollander et al. (2001) noted that patients with LCA8 carried null alleles more frequently than did patients with RP12.

In all 4 affected members of a Middle Eastern family with LCA8 with high to extreme hyperopia, Abouzeid et al. (2006) found linkage of the disorder to 1q31 and identified homozygosity for a mutation in the CRB1 gene (G1103R; 604210.0011). Abouzeid et al. (2006) showed that hyperopia and LCA were linked to the mutant CRB1 gene itself and were not dependent on unlinked modifiers. Abouzeid et al. (2006) noted that the G1103R mutation had previously been identified in compound heterozygous state in a patient with sporadic LCA by Hanein et al. (2004).