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)
One of the major clinical characteristics of congenital stationary night blindness(CSNB)is dysfunction of rod photoreceptors of the retina.Rhodopsin,the photosensitive pigment of the rods,is essential for maintaining the normal function of rod photoreceptors.It is resonable to hypothesize that mutations or deletions of rhodopsin gene may be involved in the molecular defect of CSNB.To test this hypothesis,we are searching for rhodopsin gene mutations in patients with autosomal dominant CSNB.In this study,DNA fragments containing the coding sequences in exon 5 of rhodopsin gene were amplified by polymerase chain reaction(PCR)in 15 patients and 5 unaffected members from a large family with autosomal dominant CSNB.RFLP analysis of these DNA fragments demonstrated that in comparison with a control group of 12 normal persons,there is no obvious deletion in exon 5 of rhodopsin gene,and that mutations or deletions do not exist in codon 314,codon 347,and the third base of codon 313 as well as the first base of codon 348 of the rhodopsin gene in these CSNB patients,which suggest the molecular pathogenesis of autosomal dominant CSNB not involve mutations or deletions of these codons of the rhodopsin gene. （Chin J Ocul Fundus Dis,1993,9:66-69）
ObjectiveTo determine the pathogenic gene mutation in a family with incomplete congenital quiescent night blindness (CSNB) of Schubert-Bornschein type. MethodsA retrospective clinical study. In February 2021, one patient and his parents and elder brother from a Han Chinese incomplete CSNB of Schubert-Bornschein type family diagnosed by clinical and genetic examination at Henan Provincial People's Hospital were included in the study. The patient’s medical history, family history were inquired; best corrected visual acuity (BCVA), color vision, fundus color photography, full-field electroretinogram (ERG), and frequency domain optical coherence tomography (OCT) were examined in detail. Five ml of the subject’s peripheral venous blood was collected and the whole genome DNA was extracted. The genomic DNA of the subject was library constructed, and all-exon probes were polymerized for capture. The suspected pathogenic mutation site was verified by Sanger, and the pathogenicity of the gene mutation site was determined by parallel bioinformatics analysis. ResultsThe BCVA of both eyes of the proband (Ⅱ2) was 0.4; the color vision test could not recognize the red color. Fundus examination showed no obvious abnormalities. The retina thickness in the macular area of both eyes was slightly thinned. ERG examination of the whole field showed that the amplitude of ERG b wave was significantly reduced under the stimulation of binocular dark adaptation 3.0 and showed a negative waveform. The mother of the proband (Ⅰ2) had normal BCVA, color vision, fundus color photography, and frequency domain OCT examination. The full-field ERG examination showed that the amplitude of each eye reaction was slightly reduced, and the amplitude of the dark adaptation shock potential was significantly reduced. Genetic testing showed that the proband (Ⅱ2) had a c.1761dupC hemizygous mutation in exon 14 of the voltage-dependent calcium channel α1F subunit gene (CACNA1F gene). The results of protein sequence homology analysis showed that the site was highly conserved in multiple species; the results of bioinformatics analysis showed that the CACNA1F gene c.1761dupC (pY588fs) subsequently had a frameshift mutation and became a stop at position 10. Codons appear translational termination in the conserved regions of the protein. According to the standards and guidelines of the American College of Medical Genetics and Genomics, the mutation was judged to be a possible pathogenic variant. The mother of the proband (Ⅰ2) was a carrier of this site mutation. The clinical and genetic test results of the father and elder brother of the proband were not abnormal. ConclusionCACNA1F gene c.1761dupC is the pathogenic mutation site of the Schubert-Bornschein type incomplete CSNB family.
Objective To observe the clinical phenotype of patients with CACNA1F gene variant. MethodsA retrospective clinical study. From January 1, 2022 to October 1, 2023, 36 patients with CACNA1F gene mutation-related eye diseases diagnosed by clinical examination and genetic testing in Changsha Aier Eye Hospital and Jinan Purui Eye Hospital were included in the study. All patients underwent best-corrected visual acuity (BCVA), medical optometry, fundus color photography, optical coherence tomography, full-field electroretinography (ERG), nystagmus examination, and genetic whole-exon sequencing. BCVA was performed using log visual acuity charts and converted to (logMAR). The nystagmus examination was performed using a helmet-mounted multifunctional video eye movement recording system. The clinical phenotypic characteristics were observed. Results At total of 36 patients were male, aged was (6.69±5.26) years. There were 36 cases of myopia (38.89%, 14/36), and the spherical equivalent was (−3.01±4.84) D. There were 14 different genetic variants including 7 cases of pathogenic variants, 20 cases of suspected pathogenic variants and 9 cases of unknown pathogenic variants, respectively. logMAR BCVA was 0.67±0.27; 26 patients had optic nerve atrophy (72.22%, 26/36); 6 had optical nerve hypoplasia (16.67%, 6/36). Fundus pigment dysplasia with mild iris transillumination was found in 4 cases (11.11%, 4/36). There were 5 cases of foveal dysplasia (Thomas grade) 1 (13.89%, 5/36). In full-field ERG examination, the B-wave reduction of the maximum mixed reaction of dark adaptation showed a negative waveform, and the amplitude of the shock potential was seriously reduced. The main phenotypes were residual type (residual dark adaptation 0.01 reaction wave and bright adaptation 3.0 reaction wave, and the response decreased at 30 Hz to a double-peak wide wave), dominant type of bright adaptation decreased (all light adaptation extinguished, all dark adaptation extinguished), and total extinction type (all light adaptation extinguished). Among them, 10 cases presented with residual ERG (27.78%, 10/36), 8 cases with photopic reduced ERG (22.22%, 8/36) and 18 with extinguished ERG (50.00%, 18/36). Low amplitude and high frequency pendulum (PLAHF) nystagmus waverforms were found in 32 cases (88.89%, 32/36), head oscillation in 27 cases (75.00%, 27/36) and chin up abnormal head posture in 26 cases (72.22%, 26/36), respectively. ConclusionsCACNA1F Gene variant eye diseases had diverse clinical phenotype. Clinical phenotype of PLAHF nystagmus is closely related with CACNA1F gene variant eye disease.