Objective To make the diagnosis of a pedigree of X-linked congenital stational night blindness(CSNB) and to identify the disease-causing gene. Methods Clinical examination and family analysis were made. Venous blood was drawn from 5 affected and 16 unaffected individuals from the family. Genomic DNA was extracted. The locus of the candidate gene was mapped by linkage study. Mutation was screened by polymerase chain reaction (PCR) of the candidate gene exons and flanked introns. The PCR products are directly sequenced. The healthy people in and out of the family who were selected according to certain standards were as the control. Results A Chinese family with X-linked complete congenital stationary night blindness (CSNB1) was diagnosed. A missense mutation A772C (T258P) in exon 2 of NYX gene was identified in all affected patients and all female carriers were heterozygous. This mutation was neither found in normal family members nor among 110 unrelated normal controls. Conclusion A novel mutation of NYX gene with threonine to proline change is responsible for this Chinese CSNB1 family. (Chin J Ocul Fundus Dis, 2007, 23: 184-188)
Usher syndrome (USH) is an autosomal recessive hereditary disease, characterized as retinitis pigmentosa and deafness. According to the severity of hearing loss, presence or absence of vestibular dysfunction, Usher syndrome is divided into 3 clinical subtypes: USH1, USH2 and USH3. Due to the genetically heterogeneous, it is important and valuable to find out the gene mutations in USH patients, which will be helpful to prenatal diagnosis, early intervention and gene therapy. Till now, the following 13 USH-related chromosomal loci were reported in the literature: USH1B, USH1C, USH1D (CDH23 gene), USH1F (PCDH15 gene), USH1G (SANS gene), USH1E, USH1H, USH1J and USH1K, USH2A, USH2C, USH2D and USH3 (CLRN1 gene). Ten out of all 13 loci have been located and identified. But more mechanisms should be further investigated, such as the relationship between the locus of gene mutations and clinical symptoms, how the modified protein structures and functions trigger clinical symptoms.
ObjectiveTo observe the gene mutations and clinical phenotypes in patients with Usher syndrome type 2 (USH2) and retinitis pigmentosa (RP).Methods From August 2018 to January 2019, 4 patients and 11 normal family members from 3 families of USH2 and RP who visited Henan Eye Hospital were enrolled in the study. Detailed medical history was obtained and visual acuity, fundus color photography, OCT, visual field, full field ERG examination were performed. Among the three families, pedigree 1 was diagnosed with USH2, pedigree 2 and pedigree 3 were diagnosed with RP. The peripheral venous blood of patients and their family members were collected, and the whole genomic DNA was extracted. Targeted capture next generation sequencing analysis was performed on these members, and Sanger sequencing and family co-segregation were verified.ResultsIn the family F1, the proband had symptoms of RP and sensorineural deafness. Sequencing revealed two heterozygous frameshift variants: c.13877-13880 del AGAC (p. Q4626P) in exon 64 and c.798 del T (p. F266L) in exon 5 of USH2A. Both patients of family 2 and 3 showed RP signs without deafness. Two heterozygous variants c.15178T＞C (p. S5060 P) in exon 70 and c.6986C＞A (p. P2329H) in exon 37, and a pathogenic heterozygous variant c.5836C＞T (p. R1946X) in exon 29 of USH2A were identified in family F2. A heterozygous missense variant c.14951C＞T (p. P4984L) in exon 68 and a variant c.11156G＞A (p. R3719H) in exon 57 of USH2A were found in family F3. The results of conservation analysis showed that the corresponding amino acid sites of USH2A p.Q4626P, p.F266L, p.S5060P, p.P2329H and p.P4984L were highly conserved in many species. Among these 7 pathogenic variants detected, M1-M4 and M6 were novel.ConclusionsMutation USH2A gene are the main cause of USH2 and non-syndromic RP. Different variants affect protein translation and synthesis, consequently causing different clinical phenotypes.