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Review
. 2022 Sep 17;15(1):197.
doi: 10.1186/s12920-022-01356-z.

A novel nonsense variant (c.1499C>G) in CRB1 caused Leber congenital amaurosis-8 in a Chinese family and a literature review

Wenhua Duan #  1 , Taicheng Zhou #  2 , Huawei Jiang  1 , Minhui Zhang  3 , Min Hu  2 , Liwei Zhang  4
Affiliations
Review

A novel nonsense variant (c.1499C>G) in CRB1 caused Leber congenital amaurosis-8 in a Chinese family and a literature review

Wenhua Duan et al. BMC Med Genomics. .

Abstract

Background: Leber's congenital amaurosis (LCA) is a severe hereditary retinopathy disease that is characterized by early and severe reduction of vision, nystagmus, and sluggish or absent pupillary responses. To date, the pathogenesis of LCA remains unclear, and the majority of cases are caused by autosomal recessive inheritance. In this study, we explored the variant in the Crumbs homologue 1 (CRB1) gene in a Chinese family with LCA.

Methods: We conducted comprehensive ocular examinations and collected 5 ml of blood samples from members of a Chinese family with LCA. A pathogenic variant was identified by capturing (the panel in NGS) and Sanger sequencing validation.

Results: A nonsense variant (c.1499C>G) in the 6th exon of CRB1 gene in a Chinese family with LCA was identified, which predicted a change in the protein p. S500*, may lead to loss of gene function. We summarized the 76 variants reported thus far in CRB1 that caused LCA8.

Conclusions: This study reported a novel variant c.1499C>G (p. S500*) of the CRB1 gene occurred in a Chinese family with LCA, thus expanding the spectrum of CRB1 variants causing LCA.

Keywords: Crumbs homologue 1 (CRB1); Leber’s congenital amaurosis; Variant.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Pedigree of the LCA family with a CRB1 variant, sequencing chromatogram, and diagnostic fundus. a Pedigree of the LCA family with a CRB1 variant. The proband is marked by an arrow, black symbols denote affected members, white symbols denote unaffected members, squares denote males, and circles denote females. b Sequencing chromatograms. The affected proband showed a homozygous variant in the CRB1 gene: nucleotide 1499 changed from a cytosine to guanine (c.1499C>G) homozygous variant, resulting in a nonsense variant of amino acids (p. S500*), her parents and sister show a heterozygous variant at the same site. c Diagnosis of the fundus. Both eyes of the proband showed pigmentation of the retina at the posterior pole that was peppery and salt-like, and the macular area was a mass of lesions with a large amount of pigmentation. d Her 5-year-old sister’s fundus is normal, and the same is true for her parents
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