Neuro-ophthalmic Study
Clinical manifestations and genetic analysis of six different families of Leber's congenital amaurosis
Bai Zhouxian, Shao Jingzhi, Chen Yibing, Kong Xiangdong
Published 2021-03-25
Cite as Chin J Ocul Fundus Dis, 2021, 37(3): 195-200. DOI: 10.3760/cma.j.cn511434-20200430-00191
Abstract
ObjectiveTo observe and analyze the pathogenic gene types and clinical phenotypes of Leber congenital amaurosis (LCA).
MethodsA retrospective clinical study. Six patients with LCA confirmed by genetic testing and 18 family members were included in the study. The patients came from six unrelated families. The family was investigated with a specific hereditary eye disease enrichment panel which contained 463 known pathogenic genes and based on targeted exome capture technology first to indentify the potential pathogenic genes and mutations. Then the TULP1 , RPGRIP1 , GUCY2D pathogenic mutations were conformed by Sanger sequencing. The pathogenicity of the gene variation was searched through relevant databases and PubMed literature, and its function was explained by protein prediction software.
ResultsOf the 6 patients, 3 were males and 3 were females; the age was from 3 to 33 years. Nystagmus, finger pressing eyes, photophobia, and night blindness were seen in 5 cases; electroretinogram showed 3 cases of extinction or near extinction; and 4 cases of retinopathy. The results showed patients with compound heterozygous mutation of c.1318C> T and c.1142T> G, homozygous mutation ofc.1318C> T and compound heterozygous mutation of c.1153G> A and c.1561C> T ofTULP1 in Family 1, Family 2 and Family 5, respectively. There were compound heterozygous mutations of RPGRIP1 c.391delG and c.1468-2A> G in Family 3 and c.715delA and c.1765C> T in Family 6, respectively. Homozygous mutation of c.3177_3178delAC ofGUCY2D was found in Family 4.The parents of all six patients were carriers of corresponding heterozygous mutations.TULP1 gene c.1142T> G,RPGRIP1 gene c.391delG, c.715delA and c.1765C> T andGUCY2D gene c.3177_3178delAC mutations were novel mutations and unreported. The 381th amino acid locus of product protein of TULP1 gene was highly conserved among species. The protein prediction software predicted that the mutation pathogenic. The c.391delG, c.715delA and c.1765C> T mutations ofRPGRIP1 gene and c.3177_3178delAC mutation of GUCY2D gene can lead to early translation termination of their product proteins, which are pathogenic variants.
ConclusionThe pathogenic mutations of TULP1, RPGRIP1 and GUCY2D genes led to LCA 15, LCA 6 and LCA 1 in six families.
Key words:
Leber congenital amaurosis/etiology; Genes; Mutation; TULP1 gene; RPGRIP1 gene; GUCY2D gene
Contributor Information
Bai Zhouxian
The Genetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
Shao Jingzhi
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
Chen Yibing
The Genetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
Kong Xiangdong
The Genetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
