Molecular Genetics & Genomic Medicine最新文献

{"title":"A Novel Compound Heterozygous Variant in the ABHD12 Gene Cause PHARC Syndrome in a Chinese Family: The Proband Presenting New Genotype and Phenotype.","authors":"Meijiao Ma, Jinhai Ma, Yuanyuan Lian, Xueli Wu, Wenming Wang, Weining Rong, Xunlun Sheng","doi":"10.1002/mgg3.70055","DOIUrl":"10.1002/mgg3.70055","url":null,"abstract":"<p><strong>Background: </strong>PHARC syndrome, a rare autosomal recessive neurodegenerative disorder caused by mutations in the ABHD12 gene, is characterized by demyelinating polyneuropathy, hearing loss, ataxia, retinitis pigmentosa (RP), and early-onset cataracts. If patients are first diagnosed in the ophthalmology department, they are easily misdiagnosed as having RP or Usher syndrome. This study aimed to identify the genetic etiology and determine the clinical diagnosis of a Chinese family with suspected PHARC syndrome.</p><p><strong>Method: </strong>Comprehensive ophthalmic examinations and systemic evaluations were conducted to confirm the phenotype. The genotype was identified through Whole Exome Sequencing (WES), and the current literature was reviewed understand better manifestations of PHARC syndrome related to pathogenic variants.</p><p><strong>Results: </strong>The principal symptoms of the proband comprised profound sensorineural hearing loss since childhood, severe visual impairment, congenital cataracts, cone-rod dystrophy, and ataxia. WES revealed that the proband carried a compound heterozygous variant in the ABHD12 gene: M1, a known nonsense variation c.477G > A (p.Trp159Ter); and M2, a novel copy number variant with a deletion of approximately 18.10 Kbp in chromosome 20p11.21 (seq[GRCh38]del(20) (p11.21)chr20:g. 25302218_25320318del), covering exons 4-12 of the ABHD12 gene. The literature review indicated that there were 65 patients with PHARC from 30 different families. All clinical information of the described patients with PHARC syndrome and all known mutations associated with the disease to date were compiled.</p><p><strong>Conclusion: </strong>This study expands the spectrum of pathogenic variants and phenotype for PHARC syndrome and suggests genetic testing is necessary for a definitive diagnosis of PHARC syndrome.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70055"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Validation of Biomarkers in Metabolic Dysfunction-Associated Steatohepatitis Using Machine Learning and Bioinformatics.","authors":"Yu-Ying Zhang, Jin-E Li, Hai-Xia Zeng, Shuang Liu, Yun-Fei Luo, Peng Yu, Jian-Ping Liu","doi":"10.1002/mgg3.70063","DOIUrl":"10.1002/mgg3.70063","url":null,"abstract":"<p><strong>Background: </strong>The incidence of metabolic dysfunction-associated steatohepatitis (MASH) is increasing annually. MASH can progress to cirrhosis and hepatocellular carcinoma. However, the early diagnosis of MASH is challenging.</p><p><strong>Aim: </strong>To screen prospective biomarkers for MASH and verify their effectiveness through in vitro and in vivo experiments.</p><p><strong>Methods: </strong>Microarray datasets (GSE89632, GSE48452, and GSE63067) from the Gene Expression Omnibus database were used to identify differentially expressed genes (DEGs) between patients with MASH and healthy controls. Machine learning methods such as support vector machine recursive feature elimination and least absolute shrinkage and selection operator were utilized to identify optimum feature genes (OFGs). OFGs were validated using the GSE66676 dataset. CIBERSORT was utilized to illustrate the variations in immune cell abundance between patients with MASH and healthy controls. The correlation between OFGs and immune cell populations was evaluated. The OFGs were validated at both transcriptional and protein levels.</p><p><strong>Results: </strong>Initially, 37 DEGs were identified in patients with MASH compared with healthy controls. In the enrichment analysis, the DEGs were mainly related to inflammatory responses and immune signal-related pathways. Subsequently, using machine learning algorithms, five genes (FMO1, PEG10, TP53I3, ME1, and TRHDE) were identified as OFGs. The candidate biomarkers were validated in the testing dataset and through experiments with animal and cell models. The malic enzyme (ME1) gene (HGNC:6983) expression was significantly upregulated in MASH samples compared to controls (0.4353 ± 0.2262 vs. -0.06968 ± 0.3222, p = 0.00076). Immune infiltration analysis revealed a negative correlation between ME1 expression and plasma cells (R = -0.77, p = 0.0033).</p><p><strong>Conclusion: </strong>This study found that ME1 plays a regulatory role in early MASH, which may affect disease progression by mediating plasma cells and T cells gamma delta to regulate immune microenvironment. This finding provides a new idea for the early diagnosis, monitoring and potential therapeutic intervention of MASH.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70063"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychological Distress and Quality of Life in Families With a Germline CDKN2A Pathogenic Variant.","authors":"A M Onnekink, D C F Klatte, J E van Hooft, S H van den Berg, S M S van der Zwaan, R van Doorn, S C H Hinnen, T P Potjer, E M A Bleiker, M E van Leerdam","doi":"10.1002/mgg3.70045","DOIUrl":"10.1002/mgg3.70045","url":null,"abstract":"<p><strong>Background: </strong>Individuals with a germline CDKN2A pathogenic variant (PV) have an increased lifetime risk of melanoma and pancreatic cancer. It is unknown whether the CDKN2A PV impacts quality of life (QoL). Therefore we aimed to assess QoL and psychological distress in families affected by the PV.</p><p><strong>Methods: </strong>This cross-sectional study included confirmed carriers and those with a 50% likelihood of carrying the PV (at-risk carriers) under cancer surveillance who were invited to complete a one-time questionnaire. Both confirmed and at-risk carriers are offered skin surveillance, whereas only confirmed carriers aged 40 years or older can participate in pancreatic surveillance.</p><p><strong>Results: </strong>In total, 59/247 (24%) individuals under skin surveillance only (skin surveillance group) and 188/290 (65%) individuals under both skin and pancreatic cancer surveillance (pancreatic surveillance group) responded. In both surveillance groups, health-related QoL and general distress levels were within the general population norms. However, more than 40% of all study participants reported melanoma-related distress. Pancreatic cancer-related distress was experienced by 45% of the pancreatic surveillance group. Determinants of cancer-related distress were a first-degree relative with melanoma or pancreatic cancer, increased cancer risk perception, and poor general health perception. Over 80% of the participants felt that the benefits of cancer surveillance outweigh the disadvantages.</p><p><strong>Conclusion: </strong>In conclusion, confirmed and at-risk carriers of the CDKN2A PV under cancer surveillance experienced similar levels of QoL and general distress compared to the general population. However, cancer-related worry was substantial in this population. These findings can help identify individuals who may benefit from psychological support.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70045"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a Novel COL4A3 Homozygous/Heterozygous Splicing Mutation on the Mild Phenotype in a Family With Autosomal Recessive Alport Syndrome and a Literature Review.","authors":"Dan Chen, Li Zhang, Jing Rao, Yan Zhou, Lujun Dai, Songsong Huang, Chunxia Yang, Qiuhan Bian, Tao Zhang, Xiaoyan Yang","doi":"10.1002/mgg3.70053","DOIUrl":"10.1002/mgg3.70053","url":null,"abstract":"<p><strong>Background: </strong>Alport syndrome involves chronic progressive kidney failure and extrarenal organ damage caused by COL4A3, COL4A4, and COL4A5 mutations.</p><p><strong>Methods: </strong>We initially discerned a COL4A3 splicing mutation via next-generation sequencing. Next, we used bioinformatics, renal biopsy pathology, and an in vitro minigene experiment. Complementary analysis of clinical data was carried out, and we explored the expression and function of the variants to verify their pathogenicity.</p><p><strong>Results: </strong>A splicing mutation (c.687 + 1G > T) in COL4A3 was found in a Chinese family. Bioinformatics analysis revealed its impact on splicing, causing a translational frameshift, which was confirmed by an in vitro minigene assay. The proband's glomerular basement membrane displayed reduced type IV collagen α3, α4, and α5 chains, with some absent, suggesting disruption of collagen IV trimers in the glomerular basement membrane, potentially damaging the glomerular filtration barrier.</p><p><strong>Conclusion: </strong>We present a novel finding of a previously unreported c.687 + 1G > T mutation in COL4A3 that disrupts transcription and translation, impairing α3α4α5 (IV) chain formation, altering the integrity of the glomerular basement membrane, causing hereditary Alport syndrome. This discovery enriches the genetic map of Alport syndrome, aiding in clinical genetic guidance, and enhancing the efficacy of prenatal testing.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70053"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss-of-Function CARS1 Variants in a Patient With Microcephaly, Developmental Delay, and a Brittle Hair Phenotype.","authors":"Christina Del Greco, Molly E Kuo, Desiree E C Smith, Marisa I Mendes, Gajja S Salamons, Marek Nemcovic, Rebeka Kodrikova, Sergej Sestak, Malina Stancheva, Anthony Antonellis","doi":"10.1002/mgg3.70078","DOIUrl":"10.1002/mgg3.70078","url":null,"abstract":"<p><strong>Background: </strong>Mutations in cysteinyl-tRNA synthetase (CARS1) have been implicated in a multisystem disease including microcephaly, developmental delay, and brittle hair and nail phenotypes.</p><p><strong>Methods: </strong>Here, we present a patient with hepatopathy, hypothyroidism, short stature, developmental delay, microcephaly, muscular hypotonia, brittle hair, and ataxia. The patient underwent exome sequencing to identify potentially pathogenic genetic variants. In addition, identified variants were assessed using yeast complementation assays to determine functional consequences.</p><p><strong>Results: </strong>Exome sequencing determined that the patient is compound heterozygous for p.Arg341His and p.Arg370Trp CARS1. Yeast complementation assays showed that the p.Arg341His variant has a hypomorphic effect and that the p.Arg370Trp variant causes a complete loss-of-function effect.</p><p><strong>Conclusion: </strong>This study is the second report of pathogenic CARS1 variants and expands the allelic and phenotypic heterogeneity of CARS1-associated disease.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70078"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carrier Screening and Prenatal Diagnosis for Spinal Muscular Atrophy in Ningde City, Fujian Province.","authors":"JiaoJiao Lu, Xian Zheng, Jing Yang, WenXu Dong, LuoYuan Cao, Xiaomei Zeng, Qinjuan Wu, Xunyan Chen, XianGuo Fu","doi":"10.1002/mgg3.70077","DOIUrl":"10.1002/mgg3.70077","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to screen for SMN1 (OMIM#600354) deletion carriers in 6035 pregnant women in the eastern part of Fujian Province, to provide a theoretical basis for genetic counseling and further prenatal diagnosis of the disease, and to explore the carrier frequency and clinical significance of spinal muscular atrophy (SMA) in the eastern part of Fujian Province.</p><p><strong>Methods: </strong>Pregnant women treated at the prenatal diagnosis institution of Ningde Municipal Hospital of Ningde Normal University from February 2022 to October 2023 were selected as research subjects. The exons 7 and 8 (E7 and E8) of the survival of motor neuron 1 gene (SMN1) from 6035 pregnant women were detected using real-time fluorescence quantitative PCR (qPCR). Spouses of pregnant women with positive results were recalled for gene detection, and prenatal diagnosis was performed for both partners as carriers.</p><p><strong>Results: </strong>A total of 100 SMA carriers were detected in 6035 pregnant women, including 98 with heterozygous deletions of E7 and E8 of the SMN1 gene and two with heterozygous deletions of E7 only. The carrier frequency was 1.66%. One couple was both identified as SMA carriers, and their fetus with a homozygous deletion of E7 and E8 of the SMN1 gene was finally detected by prenatal diagnosis and gene analysis.</p><p><strong>Conclusion: </strong>The frequency of SMA mutation in the Ningde area of Fujian province has been identified, which can provide the basis for genetic counseling and prenatal diagnosis. Interventional prenatal genetic diagnosis for high-risk fetuses can effectively prevent the birth of children with SMA and is crucial for preventing and controlling birth defects.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70077"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Severe Cortical Involvement and Novel FUCA1 Mutations in a Pediatric Fucosidosis Case.","authors":"Mar Jiménez de la Peña, Sara López-Martín, Daniel Martín Fernández-Mayoralas, Ana Laura Fernández-Perrone, Ana Jiménez de Domingo, Pilar Tirado, Beatriz Calleja-Pérez, Sara Álvarez, Jacobo Albert, Alberto Fernández-Jaén","doi":"10.1002/mgg3.70070","DOIUrl":"10.1002/mgg3.70070","url":null,"abstract":"<p><strong>Background: </strong>Biallelic pathogenic variants in the FUCA1 gene are associated with fucosidosis. This report describes a 4-year-old boy presenting with psychomotor regression, spasticity, and dystonic postures.</p><p><strong>Methods and results: </strong>Trio-based whole exome sequencing revealed two previously unreported loss-of-function variants in the FUCA1 gene. Brain magnetic resonance imaging (MRI) findings included corpus callosum hypoplasia, white matter hypomyelination, and alterations in the globus pallidi, alongside markedly reduced cortical thickness.</p><p><strong>Conclusions: </strong>These findings suggest that cortical atrophy may occur in the early stages of fucosidosis. Early diagnosis is imperative for genetic counseling, timely investigations, and initiating early therapeutic interventions to potentially mitigate more extensive brain involvement.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70070"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Late-Onset Krabbe Disease: Case Report of Two Patients in a Chinese Family and Literature Review.","authors":"Yujun Sun, Jiayuan Zheng, Lei He, Xiaojuan Li, Wenzhou Liu, Jionglin Wu, Jiajie Li, Taolue Zhou, Gang Zeng, Weidong Song, Yanbo Chen","doi":"10.1002/mgg3.70065","DOIUrl":"10.1002/mgg3.70065","url":null,"abstract":"<p><strong>Background: </strong>Krabbe disease (KD; globoid cell leucodystrophy) is a rare autosomal recessive lipid storage disorder that affects the white matter of the peripheral and central nervous. Late-onset KD is less frequently diagnosed and often presents with milder symptoms, making accurate diagnosis challenging, especially when distinguishing it from peripheral neuropathy. In this report, we present two cases of late-onset KD in a Chinese family. The first case involves a 25-year-old female who sought treatment due to long-standing spastic gait and deformities in her lower limbs. A muscle biopsy revealed muscle atrophy, and electromyography indicated neurogenic damage. Her 27-year-old sister (Case 2) exhibited similar lower limb weakness, along with more severe central and peripheral neurological symptoms.</p><p><strong>Methods: </strong>The patients' peripheral blood was retained for galactocerebrosidase (GALC) enzyme activity assaying and whole exome gene sequencing.</p><p><strong>Results: </strong>GALC enzyme activity assaying showed decreased GALC activity and gene sequencing revealed homozygous mutation of p.L634S (c.1901T>C) in the two cases.</p><p><strong>Conclusion: </strong>This study broadens the scope for considering of KD in the diagnosis of patients presenting with muscle weakness and deformities in the lower limbs.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70065"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Genetics of 241 Fetuses With Talipes Equinovarus: A 8-Year Monocentric Retrospective Study.","authors":"Pingshan Pan, Dongbing Huang, Jiangxuan Wei, Wei He, Peng Huang, Sheng Yi, Jing Huang, Dahua Meng, Shuyin Tan, Xinyan Li, Hongwei Wei, Linlin Wang","doi":"10.1002/mgg3.70076","DOIUrl":"10.1002/mgg3.70076","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate the utility of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in fetuses diagnosed with talipes equinovarus (TE), as well as to explore the genetic factors contributing to TE.</p><p><strong>Methods: </strong>The study reviewed a total of 241 fetuses with TE between January 2015 and December 2023, categorizing them into two groups based on the absence or presence of additional ultrasound anomalies: 163 cases (67.6%) in the isolated TE group and 78 cases (32.4%) in the syndromic TE group. Karyotyping and CMA were performed for all cases, with WES being performed for 18 cases that had normal karyotype and CMA results.</p><p><strong>Results: </strong>The results indicated a total detection rate of 16.2% (39/241) using karyotyping and CMA. Furthermore, the detection rates of karyotyping and CMA in the isolated TE group and syndromic TE group were 10.4% (17/163) and 28.2% (22/78) respectively, showing a statistically significant difference (p < 0.05). WES was conducted on 18 fetuses with normal karyotyping and CMA results. A total of six cases, consisting of five cases with pathogenic single nucleotide variant (SNV) and one case of variants of uncertain significance (VUS), were identified, resulting in a detection rate of 33.3% (6/18). The identified SNVs was associated with the RIT1, GNPNAT1, PEX1, RYR1, ASCC1, and GDAP1 genes. The detection rates of WES in the isolated TE group and syndromic TE group were 25% (1/4) and 35.7% (5/14) respectively, with no statistically significant difference (p > 0.05). The overall diagnostic yield of genetic testing was 18.7% (45/241) in fetuses with TE.</p><p><strong>Conclusion: </strong>When prenatal ultrasound identifies fetal TE, chromosome karyotyping and CMA should be considered as the first-line diagnostic tests. Unlike previous studies, this study recommended WES in cases of normal CMA results for both isolated and syndromic fetal TE.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70076"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Genetic and Phenotypic Landscape of a Chinese Cohort With Retinitis Pigmentosa.","authors":"He-Nan Sun, Kai-Li Du, Yan Sun, Cong Liu, Jin-Hui Xue, Xin-Xin Wang, Ye Liu, Hui-Hui Yu, Jia-Yuan Ge, Jia Rong, Di Wang, Yue Ren, Ji-Jing Pang, Jian-Kang Li, Zhuo-Shi Wang","doi":"10.1002/mgg3.70011","DOIUrl":"10.1002/mgg3.70011","url":null,"abstract":"<p><strong>Introduction: </strong>Retinitis pigmentosa (RP) is a type of inherited retinal degeneration (IRD) that typically leads to vision loss in individuals of working age. Currently, over 100 genes and loci, as well as over 1000 individual variants, have been identified in relation to RP. The aim of this study was to investigate the genetic distribution and characteristics of Chinese patients with RP, as well as to describe and analyze the genetic features of the high-frequency variant from the RPGR gene.</p><p><strong>Methods: </strong>A total of 69 Chinese patients diagnosed with RP from 36 families were included in this study. Blood samples were collected, and DNA was extracted for genetic analysis. A custom panel targeting 822 genes associated with RP was designed for next-generation sequencing (NGS) analysis. The sequenced data were processed and analyzed using bioinformatics tools to identify genetic variants. Variant classification followed the guidelines provided by the American College of Medical Genetics and Genomics (ACMG), taking into consideration functional effects, population frequencies, and previous literature reports. Variant validation was performed using Sanger sequencing to confirm the presence of identified variants. The inheritance pattern of RP-associated variants was determined by analyzing the segregation pattern within families. Pedigrees were constructed based on the clinical and genetic information of the participants. Statistical analysis was conducted to summarize the clinical characteristics of the RP patients using descriptive statistics. Ethical considerations were strictly followed throughout the study, with approval obtained from the ethics committee and informed consent obtained from all participants.</p><p><strong>Results: </strong>Following this, the identified variants were classified and subjected to statistical analysis. A total of 15 candidate genes associated with RP were identified, along with 39 variants, consisting of 36 reported variants and 3 novel variants. The majority of these variants were classified as pathogenic. The most common changes observed in this study were substitutions, followed by missense variants. Genetic analysis indicated that all variants occurred in the exon region. In the RPGR gene, half the variants are located in the ORF15. Gene, with half of variants located in ORF15. The most frequent variant within this group was RPGR NM_001034853.1: c.2236_2237del, which was identified in a large five-generation pedigree. The three novel variants reported in this study include NM_015629.3: c.1168_1169insGATTCAGCCTGGCC of PRPF31, NM_001034853.1: c.3026_3027insAGAGGGAGAGGAAGAAGG and NM_000328.2: c.611T>G of RPGR.</p><p><strong>Conclusions: </strong>The findings of this study offer valuable insights into the genetic variants responsible for RP in affected individuals, which can be utilized for genetic counseling and diagnosis. This underscores the significance of genetic testing in th","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70011"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}