Molecular Genetics & Genomic Medicine最新文献

{"title":"ERAP1 Gene Variants and Haplotypes Associated With Psoriasis Vulgaris of Han Chinese in Inner Mongolia.","authors":"Xin Li, Jia Bao, Liya Ai, Fan-Rui Yang, Bo Yu, Yan-Ping Huang, Na Li, Wen-Yuan Ding, Zhi-Qiang Sun, Xin-Xiang Lv, Jian-Wen Han","doi":"10.1002/mgg3.70021","DOIUrl":"10.1002/mgg3.70021","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the association between genetic variants of ERAP1 (OMIM: 606832) and psoriasis vulgaris (PsV) susceptibility in Inner Mongolia Han nationality.</p><p><strong>Methods: </strong>For primary screening, the subjects included 142 PsV cases and 100 healthy controls without psoriasis. The 27 exons of ERAP1 gene were sequenced to screen significant genetic variants. For the validation study, the subjects included 1030 PsV cases and 965 healthy controls. A total of 18 mutations were detected for genetic variants of significance in primary screening and previously reported genetic variants.</p><p><strong>Results: </strong>In primary screening stage, 13 genetic variants of ERAP1 showed an association with psoriasis. A total of 18 genetic variants were typed for the validation, and 12 genetic variants were associated with PsV in Inner Mongolia Han population. Stratified analysis showed significant differences in the allele frequencies of 8 ERAP1 genetic variants in cases with positive family history, and significant differences in allele frequencies among 9 ERAP1 genetic variants in patients with negative family history. A risk haplotype (TCCCTCCAGACC) was significantly associated with PsV, and the most risk haplotype was E730/K528/R127/E56.</p><p><strong>Conclusion: </strong>ERAP1 gene mutation may be associated with PsV and HLA-C*06:02 in Han nationality in Inner Mongolia. A risk haplotype of four-nonsynonymous mutation (E730/K528/R127/E56) is associated with PsV.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70021"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686955","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":"Long-Read Sequencing Identifying the Genetic Complexity of Congenital Adrenal Hyperplasia in the Pedigree.","authors":"Ximin Chen, Jing Zhao, Danhua Li, Na Xi, Danying Yi, Mengjia Yan, Yan Yin, Xueyan Wang","doi":"10.1002/mgg3.70029","DOIUrl":"10.1002/mgg3.70029","url":null,"abstract":"<p><strong>Background: </strong>High sequence homology between CYP21A2 and CYP21A1P poses challenges to genetic diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). Traditional genetic testing is unable to provide an accurate diagnosis due to the genetic complexity of CAH.</p><p><strong>Methods: </strong>Deletions, duplications, and recombination breakpoints were precisely identified by long-read sequencing (LRS).</p><p><strong>Results: </strong>This study presented a pregnant woman, a 21-OHD carrier detected by MLPA, and her husband, a normal subject also detected by MLPA. The fetus was suspected of having 21-OHD based on clinical presentations such as enlarged adrenal glands, atypical external genitalia and karyotyping of 46, XX. LRS further identified the fetus as having the most severe salt-wasting (SW) form of 21-OHD with a compound heterozygote genotype. One allele was TNXA/TNXB CH-2, while the other allele was CYP21A1P/CYP21A2 CH-8. LRS precisely determined the genotypes of the fetus's father and grandmother with duplications, which misdiagnosed by MLPA. The multidisciplinary team recommended immediate glucocorticoid and mineralocorticoid treatment for the child after birth to prevent life-threatening adrenal crisis.</p><p><strong>Conclusions: </strong>LRS provides precise diagnosis for family members with CYP21A2 deletion or duplication, improving disease management and preventing potential adrenal crises. When used in pre-pregnancy genetic testing, LRS can indicate high genetic risk and guide the appropriate therapy during pregnancy and immediately after birth.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70029"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687062","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":"Newborn Screening for Isovaleric Acidemia: Treatment With Pivalate-Generating Antibiotics Contributed to False C5-Carnitine Positivity in a Chinese Population.","authors":"Wei Zhou, Ting Huang, Huizhong Li, Maosheng Gu","doi":"10.1002/mgg3.70034","DOIUrl":"10.1002/mgg3.70034","url":null,"abstract":"<p><strong>Background: </strong>Newborn screening (NBS) for isovaleric acidemia (IVA) is implemented via tandem mass spectrometry (MS/MS), but false-positive results are still common. In addition, NBS for IVA is limited by a lack of suitable biomarkers, especially after the use of pivaloylester-containing antibiotics.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study to explore the clinical correlation between antibiotic administration and false-positive results for isovalerylcarnitine (C5).</p><p><strong>Results: </strong>A total of 509,313 newborns were recruited from the initial NBS study, only one of whom underwent genetic confirmation, conducted between 2015 and 2020. Significant associations between false-positive C5-carnitine screening results and treatment with pivalate-generating antibiotics were identified with retrospective analysis.</p><p><strong>Conclusions: </strong>The current results highlight the detrimental effects of false-positive C5-carnitine screening results. Unless the licensing of pivalate-generating antibiotics for use during the neonatal period is reconsidered, a second-tier test for C5 determination will be necessary.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70034"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648390","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":"Barriers and Facilitators to Participation in Clinical Trials Related to Familial Frontotemporal Dementia: A Qualitative Study.","authors":"David Zammitt, Emilie V Brotherhood, Caroline Fearn, Caroline Greaves, Ollie Hayes, Emma Harding, Madalena Lykourgos, Jonathan D Rohrer, Josh Stott","doi":"10.1002/mgg3.70038","DOIUrl":"10.1002/mgg3.70038","url":null,"abstract":"<p><strong>Aims: </strong>Familial frontotemporal dementia (fFTD) is an inherited neurodegenerative condition characterised by executive dysfunction, impairments in social cognition, behaviour and language. Although no disease-modifying interventions are currently available, several treatments are undergoing clinical trials. This study sought to understand the barriers and facilitators to taking part in such trials, as well as general perceptions of the treatments undergoing trial.</p><p><strong>Method: </strong>Twelve interviews took place with fourteen participants: eight individuals who were genetically at-risk of developing fFTD, two individuals diagnosed with fFTD and four spousal carers. Their views and experiences of clinical trials were explored using thematic analysis.</p><p><strong>Results: </strong>Five main themes were developed: (1) effects on the individual, (2) implications for others, (3) systemic considerations, (4) the impact of genetic status and disease progression and (5) the role of communication and understanding.</p><p><strong>Conclusions: </strong>The decision to participate in clinical trials was said to be complex, involving consideration of logistical barriers alongside health implications. Participants identified potential advantages of participating in clinical trials to be direct health benefits and the ability to help others, however risks to participants and their families' physical and psychological wellbeing were also named. Relationships between organisations and participants were consistently considered to be important, with lack of psychological care at various timepoints post diagnosis; unclear communication and expectation-setting; and inadequate organisational collaboration all identified as barriers. Participants indicated that increased health-professional interest in FTD and an associated increase in opportunities would be key facilitators for greater participation in clinical trials.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70038"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710508","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":"Variability in Disease Severity in Siblings With Homozygous Missense Variant of ADSSL1: Clinical Genetic Study and Review of Literatures.","authors":"Hui Wang, Ting Zhang, Yanming Xu, Wenhui Fan","doi":"10.1002/mgg3.70041","DOIUrl":"10.1002/mgg3.70041","url":null,"abstract":"<p><strong>Background: </strong>Distal myopathies are genetic muscle disorders caused by mutations in various genes. A study found that mutations in adenylosuccinate synthetase-like 1 (ADSSL1) are associated with distal myopathy in nine patients from six unrelated families in South Korea. Previous research showed that affected individuals experienced distal muscle weakness starting in adolescence, along with mild facial muscle weakness, slightly elevated or normal serum creatine kinase (CK) levels, and the presence of a few rimmed vacuoles in muscle fibers or minimal chronic myopathic damage. Previously reported patients in this category exhibited an early age of symptom onset and severe muscle weakness. In this study, we present a case of two sisters who share the same mutation locus but display distinct disease phenotypes.</p><p><strong>Methods: </strong>A literature review was conducted on distal myopathies in patients with ADSSL1 mutations, alongside a retrospective analysis of disease severity variability among siblings with a homozygous missense variant of ADSSL1.</p><p><strong>Results: </strong>The study focuses on two sisters with differing disease manifestations despite carrying the same genetic mutation. The older sister showed lower ability in running and jumping compared to her peers at age 7 and experienced notable muscle weakness and atrophy by age 27, whereas the younger sister remained free of symptoms at age 30.</p><p><strong>Conclusion: </strong>These findings suggest that mutations at the same locus can result in varying disease outcomes, emphasizing the complexity of predicting disease progression based solely on genetic mutations.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70041"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716560","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":"Molecular Pathology of Myotonic Dystrophy Type 1 in Iceland.","authors":"E G Hallgrímsdóttir, H Svansson, V F Stefánsdóttir, Ó Á Sveinsson, H Ólafsdóttir, E Briem, S Sveinbjörnsdóttir, J J Jónsson","doi":"10.1002/mgg3.70013","DOIUrl":"10.1002/mgg3.70013","url":null,"abstract":"<p><strong>Background: </strong>Myotonic Dystrophy type 1 (DM1) is an autosomal dominant disease with anticipation due to increased number of CTG repeats in the DMPK gene.</p><p><strong>Methods: </strong>This retrospective, cohort study in Iceland assessed prevalence of DM1, molecular pathology, and patient ascertainment. Data was collected from all major hospitals in Iceland, Medical Director of Health, and independent clinics. Cohort criteria were diagnosis of DM1 on January 1, 2021, or time of death. Population-based Icelandic Genealogy Database of the Genetical Committee at the University of Iceland was used for genealogy.</p><p><strong>Results: </strong>In Iceland, 221 individuals, including 19 obligate carriers, had been diagnosed with DM1 of which 144 were alive giving a point prevalence of 39 per 100,000 (four times the world average of 9.3). Genealogy analysis identified 45 first-degree families. Age-adjusted prevalence ranged between 11 and 66 per 100,000. Average potential years of life lost were 20.5 per person. Where information was available, 63% of ascertainment was based on family history in cascade testing.</p><p><strong>Conclusion: </strong>The differences in age-adjusted prevalence suggest that the overall point prevalence is an underestimation due to underdiagnosis in younger age groups and lethality in oldest age group. Our data supports use of cascade testing to improve DM1 ascertainment.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 10","pages":"e70013"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381284","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":"Genomic Correlation, Shared Loci, and Causal Relationship Between Bullous Pemphigoid and Atopic Dermatitis: A Large-Scale Genome-Wide Cross-Trait Analysis.","authors":"Qing Wang, Xuehua Wang, Qizhen Zhuang, Yuan Wu, Junhong Zhang, Yue Lu, Jingjing Wu, Juanjuan Liu, Xiangyu Hu, Ling Han","doi":"10.1002/mgg3.70022","DOIUrl":"https://doi.org/10.1002/mgg3.70022","url":null,"abstract":"<p><strong>Background: </strong>Bullous pemphigoid (BP) and atopic dermatitis (AD) are currently thought to be tightly related, yet studies of the mechanisms of co-morbidities are lacking.</p><p><strong>Methods: </strong>We obtained GWAS data for BP (N = 376,274) and AD (N = 796,661) from the Finnish Genetic Research Program dataset and the UK Biobank, separately. Then, the following four analyses were performed: (1) cross-trait linkage disequilibrium score regression (LDSC) to assess the genetic correlation between BP and AD, (2) cross-phenotype association analysis (CPASSOC) to identify multiple effector loci shared by BP and AD, (3) transcriptome-wide association study (TWAS) to determine whether their cross-organizational expression patterns share genes with a common biological mechanism of relevance, and (4) bidirectional Mendelian randomization (MR) analysis to assess bidirectional causal effects of BP and AD.</p><p><strong>Results: </strong>We found a positive genetic association between BP and AD (rg = 0.5476, p = 0.0495) as well as identified four pleiotropic loci and 59 common genes affecting BP and AD. Bidirectional MR analysis suggested that BP promotes the risk of AD.</p><p><strong>Conclusions: </strong>We revealed a genetic link between BP and AD, which is associated with biological pleiotropy and causality. Awareness of the association between BP and AD helps dermatologists manage patients with these illnesses.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 10","pages":"e70022"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470297","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":"Deep Sequencing and Phenotyping in an Australian Tuberous Sclerosis Complex \"No Mutations Identified\" Cohort.","authors":"Clara W T Chung, Adam M Bournazos, Lok Chi Denise Chan, Vanessa Sarkozy, John Lawson, Sean E Kennedy, Sandra T Cooper, Edwin P Kirk, David Mowat","doi":"10.1002/mgg3.70017","DOIUrl":"10.1002/mgg3.70017","url":null,"abstract":"<p><p>Tuberous sclerosis complex (TSC) is a variable multisystem disorder. The \"no mutations identified\" (NMI) group are reportedly phenotypically milder than those with an identified molecular cause, and often have mosaic or intronic variants not detected by standard sequencing methods.</p><p><strong>Methods: </strong>We describe the phenotypes in an Australian TSC NMI group (n = 18) and a molecular testing strategy implementable in a diagnostic laboratory. Massively parallel sequencing (MPS) of the whole genomic regions of TSC1 and TSC2 was performed using DNA extracted from multiple tissue samples per participant.</p><p><strong>Results: </strong>Our study showed that the phenotype in TSC NMI individuals can be similar to those with heterozygous, particularly TSC1, variants. Although neurodevelopmental outcomes can be less severe, the number of organ systems involved was similar to the non-mosaic groups. A diagnostic yield of 72% (13/18) was achieved, with the majority (10/13) being mosaic variants and the remainder heterozygous variants missed on previous testing.</p><p><strong>Conclusion: </strong>Testing DNA from multiple tissue samples allowed for validation of otherwise discarded low-level mosaic variants and detection of mosaic variants by MPS without excessive cost or the need for specialised techniques. Implementing this approach in a diagnostic setting is viable and allows optimal clinical care of patients with NMI TSC.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 10","pages":"e70017"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350297","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":"Atypical Presentation of Congenital Insensitivity to Pain With Anhidrosis Leading to Diagnostic Odyssey.","authors":"Tomoyasu Higashimoto, Martin E Garber, Lauren Hipp, Jenna Damon, Qing Li","doi":"10.1002/mgg3.70027","DOIUrl":"10.1002/mgg3.70027","url":null,"abstract":"<p><strong>Background: </strong>Congenital insensitivity to pain with anhidrosis (CIPA) (OMIM 256800) is a rare autosomal-recessive condition, also known as hereditary sensory and autonomic neuropathy type IV (HSAN-IV). The most commonly reported features include anhidrosis, intellectual disability, self-mutilation, febrile episodes, impaired temperature perception, recurrent infections and/or autonomic nervous system impairment. Major joint destruction and joint deformity known as Charcot (neuropathic) joints are also seen in CIPA patients attributed to insensitivity to joint pain.</p><p><strong>Methods: </strong>We present a case of a 46-year-old female affected with CIPA with a known NTRK1 variant and previously unidentified variant. Minigene reporter constructs were generated encompassing the exon 8 to exon 13 of the NTRK1 gene using the reference sequence and one harboring c.1483 + 5G > A variant identified in our proband. Minigene constructs were transfected into HEK293T cells, and the transcript was analysed for splicing to evaluate the effect of this variant in splicing.</p><p><strong>Results: </strong>The patient (46-year-old female) exhibited right ankle joint deformity around 5 years of age. Patient also experienced lumbar compression and knee damage in adulthood. She had undergone a significant number of evaluations without clear diagnosis. Her presentation lacked many of the common clinical presentations of CIPA, and therefore, the focus of her evaluation was directed towards her unexplained joint deformities. Exome sequencing revealed a known pathogenic variant in NTRK1 (c.851 - 33T > A:p.? [Intron 7]) and a novel NTRK1 variant (c.1483 + 5G > A:p.? [Intron 11]), which was later re-classified as likely pathogenic. The patient was started on a biologic disease-modifying anti-rheumatic medication (bDMARD) due to a possible inflammatory etiology of her joint deformity. Molecular diagnosis allowed for modification of her treatment and surveillance strategies. Our minigene splicing assay demonstrated that the presence of the c.1483 + 5G > A variant has a negative effect on splicing, supporting the pathogenicity of this novel variant.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 10","pages":"e70027"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504414","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 of Pathogenic Copy Number Variants in Mexican Patients With Inherited Retinal Dystrophies Applying an Exome Sequencing Data-Based Read-Depth Approach.","authors":"Gerardo E Fabian-Morales, Vianey Ordoñez-Labastida, Froylan Garcia-Martínez, Luis Montes-Almanza, Juan C Zenteno","doi":"10.1002/mgg3.70019","DOIUrl":"https://doi.org/10.1002/mgg3.70019","url":null,"abstract":"<p><strong>Background: </strong>Retinal dystrophies (RDs) are the most common cause of inherited blindness worldwide and are caused by genetic defects in about 300 different genes. While targeted next-generation sequencing (NGS) has been demonstrated to be a reliable and efficient method to identify RD disease-causing variants, it doesn't routinely identify pathogenic structural variant as copy number variations (CNVs). Targeted NGS-based CNV detection has become a crucial step for RDs molecular diagnosis, particularly in cases without identified causative single nucleotide or Indels variants. Herein, we report the exome sequencing (ES) data-based read-depth bioinformatic analysis in a group of 30 unrelated Mexican RD patients with a negative or inconclusive genetic result after ES.</p><p><strong>Methods: </strong>CNV detection was performed using ExomeDepth software, an R package designed to detect CNVs using exome data. Bioinformatic validation of identified CNVs was conducted through a commercially available CNV caller. All identified candidate pathogenic CNVs were orthogonally verified through quantitative PCR assays.</p><p><strong>Results: </strong>Pathogenic or likely pathogenic CNVs were identified in 6 out of 30 cases (20%), and of them, a definitive molecular diagnosis was reached in 5 cases, for a final diagnostic rate of ~17%. CNV-carrying genes included CLN3 (2 cases), ABCA4 (novel deletion), EYS, and RPGRIP1.</p><p><strong>Conclusions: </strong>Our results indicate that bioinformatic analysis of ES data is a reliable method for pathogenic CNV detection and that it should be incorporated in cases with a negative or inconclusive molecular result after ES.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 10","pages":"e70019"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470298","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}