Dataset Information

Genotype-Phenotype Analysis and Mutation Spectrum in a Cohort of Chinese Patients With Congenital Nystagmus.

ABSTRACT: Purpose: Congenital nystagmus (CN) is a genetically and clinically heterogeneous ocular disorder that manifests as involuntary, periodic oscillations of the eyes. To date, only FRMD7 and GPR143 have been reported to be responsible for causing CN. Here, we aimed to identify the disease-causing mutations and describe the clinical features in the affected members in our study. Methods: All the subjects underwent a detailed ophthalmic examination. Direct sequencing of all coding exons and splice site regions in FRMD7 and GPR143 and a mutation assessment were performed in each patient. Results: We found 14 mutations in 14/37 (37.8%) probands, including nine mutations in the FRMD7 gene and five mutations in the GPR143 gene, seven of which are novel, including c.284G>A(R95K), c.964C>T(P322S), c.284+10T>G, c.901T>C (Y301H), and c.2014_2023delTCACCCATGG(S672Pfs^*12) in FRMD7, and c.250+1G>C, and c.485G>A (W162^*) in GPR143. The mutation detection rate was 87.5% (7/8) of familial vs. 24.1% (7/29) of sporadic cases. Ten mutations in 24 (41.7%) non-syndromic subjects and 4 mutations in 13(30.8%) syndromic subjects were detected. A total of 77.8% (7/9) of mutations in FRMD7 were concentrated within the FERM and FA domains, while all mutations in GPR143 were located in exons 1, 2, 4 and 6. We observed that visual acuity tended to be worse in the GPR143 group than in the FRMD7 group, and no obvious difference in other clinical manifestations was found through comparisons in different groups of patients. Conclusions: This study identified 14 mutations (seven novel and seven known) in eight familial and 29 sporadic patients with congenital nystagmus, expanding the mutational spectrum and validating FRMD7 and GPR143 as mutation hotspots. These findings also revealed a significant difference in the screening rate between different groups of participants, providing new insights for the strategy of genetic screening and early clinical diagnosis of CN.

SUBMITTER: Wang XF

PROVIDER: S-EPMC7958879 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Genotype-Phenotype Analysis and Mutation Spectrum in a Cohort of Chinese Patients With Congenital Nystagmus.

Wang Xiao-Fang XF Chen Hui H Huang Peng-Juan PJ Feng Zhuo-Kun ZK Hua Zi-Qi ZQ Feng Xiang X Han Fang F Xu Xiao-Tao XT Shen Ren-Juan RJ Li Yang Y Jin Zi-Bing ZB Yu Huan-Yun HY

Frontiers in cell and developmental biology 20210219

Purpose: Congenital nystagmus (CN) is a genetically and clinically heterogeneous ocular disorder that manifests as involuntary, periodic oscillations of the eyes. To date, only FRMD7 and GPR143 have been reported to be responsible for causing CN. Here, we aimed to identify the disease-causing mutations and describe the clinical features in the affected members in our study. Methods: All the subjects underwent a detailed ophthalmic examination. Direct sequencing of all ...[more]

PMID: 33732697

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Project description:BackgroundProgressive pseudorheumatoid dysplasia (PPRD) is a rare genetic disease with autosomal recessive inheritance. There was a lack of genotype-phenotype correlation data from the Chinese population. This study aimed to identify the genotype and phenotype characteristics of Chinese PPRD patients and to conduct a genotype-phenotype analysis of Chinese PPRD patients.MethodsGenetic analysis was performed for suspected PPRD patients from Peking Union Medical College Hospital. Medical records were collected from the electronic medical record system and patient-held portable health records. Published Chinese PPRD cases were gathered from both international and Chinese local databases. We collected demographic information, genetic variants, clinical manifestations, and imaging characteristics for further analysis.ResultsWe included 105 Chinese PPRD patients in the current study. Thirty-three variants, including nine novels and five hotspot variants, were identified, with 26/33 (79%) variants exclusively seen in the Chinese population. Chinese PPRD patients share a phenotype similar to that in international reports. Joint involvement may progress with age (R2 = 0.2541). Long bone shortening and severe deformities occur in three patients with biallelic null variants, of which at least one variant is located in exon 2. Among hotspot variants, c.624dupA (p.C209Mfs*21) were associated with later onset and more involved joints. Elbow joints were more likely to be affected in patients carrying c.624dupA (p.C209Mfs*21) and c.866dupA (p.S209Efs*13). Shoulder joints are more likely to be involved in patients with biallelic null variants (P = 0.027).ConclusionsChinese PPRD patients share a unique mutation spectrum. Among the five hotspot variants, c.624dupA is associated with later onset of disease, more extensive joint involvement, and a tendency to affect elbow joints. Biallelic null variants with at least one variant in exon 2 could be a likely cause of long bone shortening and severe deformities.

Project description:Congenital hypothyroidism (CH) is a common neonatal endocrine disorder that is characterized by irreversible neurodevelopmental and growth retardation due to insufficient biosynthesis of thyroid hormones at birth. Determining the causative genetic variants in infants is important for neonatal management. It was aimed to evaluate the variant frequencies and spectrum of CH in the neonatal population of Foshan, China. A total of 105 unrelated patients with CH and 138 controls from a neonatal screening program in Foshan, China were selected. A multiplex PCR amplification-based capture panel was performed which targeted the exon regions of 30 CH-related genes. Next-generation sequencing data were processed using an in-house bioinformatics system. A total of 91 variants distributed across 16 genes were identified in 74.29% (78/105) of the patients, of which 16 were novel variants and 75 were known variants. The most frequently mutated gene was DOUX2, followed by TG, TSHR and TPO. Specifically, DUOX2 variants p.Lys530Ter, p.Arg683Leu, p.Arg1110Gln, and IVS28 + 1G>T were highly recurrent in the cohort of the present study. Bi-allelic variants in DUOX2, TSHR and TPO were identified in 24.76% (26/105) of the patients. Monoallelic variants were identified in 28.57% (30/105) of the patients. Oligogenic variants were identified in 19.05% (20/105) of the patients. The most common variant combinations of oligogenic variants were DUOX2 and TG, and DUOX2 and SLC26A4. In addition, 2 patients harbored tri-allelic and tetra-allelic variants in DUOX2, respectively. In conclusion, DUOX2, TG, TSHR and TPO variants were the most common genetic defects in patients with CH in the neonatal population of Foshan. Specifically, biallelic DUOX2 variants were highly prevalent in the cohort. Further, the investigation provided a variant spectrum of CH-related genes and identified novel variants, which may allow for an improved understanding of the underlying genetic etiology of CH and provide evidence for further molecular epidemiological investigations that can guide preventive and therapeutic programs.

Dataset Information

Genotype-Phenotype Analysis and Mutation Spectrum in a Cohort of Chinese Patients With Congenital Nystagmus.

Publications

Genotype-Phenotype Analysis and Mutation Spectrum in a Cohort of Chinese Patients With Congenital Nystagmus.

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