Molecular Genetics & Genomic Medicine最新文献_第3页

Identification of rare missense variants in the BSN gene co-segregating with chronic otitis media in a consanguineous Pakistani family. 在一个巴基斯坦近亲家庭中发现与慢性中耳炎共存的 BSN 基因罕见错义变异。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-01 DOI: 10.1002/mgg3.2478

Ayesha Yousaf, Sairah Yousaf, Asra S Shabbir, Rafia Yousaf, Saima Riazuddin, Rehan S Shaikh, Regie Lyn P Santos-Cortez, Zubair M Ahmed

{"title":"Identification of rare missense variants in the BSN gene co-segregating with chronic otitis media in a consanguineous Pakistani family.","authors":"Ayesha Yousaf, Sairah Yousaf, Asra S Shabbir, Rafia Yousaf, Saima Riazuddin, Rehan S Shaikh, Regie Lyn P Santos-Cortez, Zubair M Ahmed","doi":"10.1002/mgg3.2478","DOIUrl":"10.1002/mgg3.2478","url":null,"abstract":"Background: Otitis media (OM) is the most frequent and complex middle ear condition with multifactorial etiology including genetic predisposition. OM depicts a variable clinical spectrum, leading to speech, developmental delay, and hearing loss. Here, we report the clinical and genetic findings of chronic suppurative otitis media (CSOM) segregating in a six-generation consanguineous Pakistani family PKOM08.Methods: Clinical evaluations, including audio and tympanometry, were conducted to assess OM manifestation and their impact on hearing function. Exome sequencing was performed to identify potential genetic variants underlying CSOM in the study participants.Results: Clinical evaluation of participating individuals revealed varying degrees of disease severity, with mild to moderate hearing loss. All the affected individuals had CSOM with no other apparent comorbidity. Whole exome followed by Sanger sequencing revealed two rare heterozygous variants [c.1867C>T, p.(Pro623Ser) and c.11015G>A, p.(Arg3672Gln)] of BSN gene in most of the affected individuals of family PKOM08. BSN encodes a scaffold bassoon protein involved in synaptic vesicle trafficking. The identified variants replaced evolutionary conserved amino acid residues in the encoded protein and are predicted to impact the ionic interactions in the secondary structure.Conclusion: A deep intronic variant of BSN has been previously implicated in the etiology of childhood ear infections. Our study further supports a link between BSN-impaired function and ear infection and CSOM in children.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291531","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}

引用次数: 0

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-01 DOI: 10.1002/mgg3.70010

Rebecca Finnegan, Mary O'Regan, Máire White, Gianpiero L Cavalleri, Norman Delanty, Katherine A Benson, Marie T Greally

{"title":"Similarity of Phenotype in Three Male Patients With the c.320A>G Variant in ALG13: Possible Genotype-Phenotype Correlation.","authors":"Rebecca Finnegan, Mary O'Regan, Máire White, Gianpiero L Cavalleri, Norman Delanty, Katherine A Benson, Marie T Greally","doi":"10.1002/mgg3.70010","DOIUrl":"10.1002/mgg3.70010","url":null,"abstract":"Background: Congenital disorders of glycosylation (CDG) are a group of neurometabolic diseases that result from genetic defects in the glycosylation of proteins and/or lipids. Multiple pathogenic genes contribute to the varying reported phenotypes of individuals with CDG-1 syndromes, most of which are inherited as autosomal recessive traits, although X-linked inheritance has also been reported. Pathogenic variants in the asparagine-linked glycosylation 13 homolog (ALG13) gene have been implicated in the aetiology of developmental and epileptic encephalopathy (DEE) 36 (OMIM:*300776, DEE36). The NM_001099922.3:c.320A>G; p.(Asn107Ser) variant is the most frequently described pathogenic variant in ALG13, with 59 females and 2 males with this variant reported to date.Methods: We report on a male with a de novo, hemizygous variant in ALG13: c.320A>G; p.(Asn107Ser), whose phenotype resembles that of two previously reported males with the same variant.Results: All three males have a de novo mutation, infantile spasms, DEE, drug-resistant epilepsy, intellectual disability, dysmorphic findings, recurrent infections, skeletal anomalies, brain abnormalities and a movement disorder: a phenotype not consistently reported in males with other pathogenic variants in ALG13.Conclusion: The similarity of phenotype in the three males with the c.320A>G variant in ALG13, suggests a possible genotype-phenotype correlation.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291533","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}

引用次数: 0

Clinical Features and Novel Pathogenic Variants of Chinese Patients With McLeod Syndrome and Chorea-Acanthocytosis. 麦克劳德综合征和舞蹈症-黄细胞增多症中国患者的临床特征和新的致病变异。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-01 DOI: 10.1002/mgg3.70015

Hao Yu, Ling Li, Xiaoyan Li, Haipeng Liu

{"title":"Clinical Features and Novel Pathogenic Variants of Chinese Patients With McLeod Syndrome and Chorea-Acanthocytosis.","authors":"Hao Yu, Ling Li, Xiaoyan Li, Haipeng Liu","doi":"10.1002/mgg3.70015","DOIUrl":"10.1002/mgg3.70015","url":null,"abstract":"Background: McLeod syndrome (MLS) and chorea-acanthocytosis (ChAc) are exceedingly rare diseases characterized by a variety of movement disorders including chorea, dystonia, and Parkinsonism. Genetic analysis plays a key role in early and accurate diagnosis, but relevant variants are still under investigation. This study aims to explore new pathogenic variants in Chinese patients with MLS and ChAc and to conduct a comprehensive analysis of the clinical heterogeneity among these patients.Methods: Eighteen Chinese patients who presented with choreatic movements with negative HTT genetic testing were identified and underwent targeted next-generation sequencing, verified by Sanger sequencing.Results: Two novel XK variants (c.970A>T, c.422_423del) were identified in three index MLS patients and six novel VPS13A variants (c.9219C>A, c.3467T>A, c.4208dup, c.9243_9246del, c.5364del, c.556-290_697-483del) in five index ChAc patients. One copy number variant of VPS13A (g.79827595_79828762del/c.556-290_697-483del) was firstly described in Chinese population.Conclusion: As the currently largest descriptive study of MLS and ChAc patients in China, this study expands on the clinical and genetic spectrum of XK and VPS13A, contributing to the clinical diagnosis of MLS and ChAc.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350296","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}

引用次数: 0

Novel compound heterozygous variants in MARVELD2 causing autosomal recessive hearing loss in two Chinese families. 两个中国家庭中导致常染色体隐性听力损失的新型 MARVELD2 复合杂合变异。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-08-01 DOI: 10.1002/mgg3.2502

Xinyu Shi, Xiaozhou Liu, Yanjun Zong, Zhengdong Zhao, Yu Sun

{"title":"Novel compound heterozygous variants in MARVELD2 causing autosomal recessive hearing loss in two Chinese families.","authors":"Xinyu Shi, Xiaozhou Liu, Yanjun Zong, Zhengdong Zhao, Yu Sun","doi":"10.1002/mgg3.2502","DOIUrl":"10.1002/mgg3.2502","url":null,"abstract":"Background: Hereditary hearing loss is an important component of congenital hearing loss. MARVELD2 (OMIM ID:610572), located in the DFNB49 locus, which encodes a tight junction protein tricellulin playing an important role in the sensory epithelial barrier of the inner ear, may contribute to nonsyndromic autosomal recessive hereditary hearing loss.Methods: Two Han Chinese pedigrees with hearing loss underwent clinical and genetic analyses. Variants were detected by targeted next-generation sequencing and sequencing data were compared with the Human Genome Reference (GRCh 37/hg 19) to identify mutant genes and loci. Furthermore, online tools such as RDDC, SpliceAI, and REVEL were used to predict risks from different variants.Results: Both two probands failed neonatal hearing screening and were diagnosed with sensorineural hearing loss. A total of 3 mutations were detected in the two families, c.1331+1G>A, c.1325A>G, and c.782G>A. According to ACMG/AMP guidelines, they were judged to be pathogenic, uncertain significance, and uncertain significance, respectively.Conclusions: These findings contribute to a better understanding of the relationship between different variants of MARVELD2 and hearing. This could further expand the spectrum of deafness gene mutations and contribute to deafness patient management and genetic counseling.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792931","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}

引用次数: 0

Genetic testing and new variants in diagnosis of congenital ichthyoses. 先天性鱼鳞病诊断中的基因检测和新变异。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-08-01 DOI: 10.1002/mgg3.70000

Milja Salo, Teija Kimpimäki, Heini Huhtala, Tanja Saarela

{"title":"Genetic testing and new variants in diagnosis of congenital ichthyoses.","authors":"Milja Salo, Teija Kimpimäki, Heini Huhtala, Tanja Saarela","doi":"10.1002/mgg3.70000","DOIUrl":"10.1002/mgg3.70000","url":null,"abstract":"Background: The aim of this study was to evaluate how diagnostic practice in congenital ichthyoses has evolved during the years 2000-2020 and what kind of gene variants of congenital ichthyosis have been found.Methods: The study cohort of this register-based research consisted of a total of 88 patients, whose diagnostic testing was conducted, and ichthyosis diagnoses set at the Department of Dermatology and the Department of Clinical Genetics at Tampere University Hospital during the years 2000-2020.Results: Diagnosis of ichthyosis was confirmed with genetic testing in 33 cases, and with conventional diagnostic methods, such as clinical findings, skin biopsy and family history of ichthyoses, in 55 cases. We observed four novel variants in patients with the clinical diagnoses of congenital ichthyoses.Conclusion: When genetic testing became available, it was offered primarily to patients with severe forms of ichthyosis. During the study period next-generation sequencing became the genetic testing method of choice providing new opportunities in diagnostics.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073326","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}

引用次数: 0

Correction to "Analysis of the clinical and genetic characteristics of a Chinese family with osteogenesis imperfecta type I". 对 "一个中国成骨不全症 I 型家族的临床和遗传特征分析 "的更正。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-08-01 DOI: 10.1002/mgg3.2497

引用次数: 0

Genetics healthcare providers' experiences counseling patients with results from consumer genomic testing. 遗传学医疗服务提供者就消费者基因组检测结果为患者提供咨询服务的经验。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-08-01 DOI: 10.1002/mgg3.2508

Magan Trottier, Dina Green, Hannah Ovadia, Amanda Catchings, Julia Gruberg, Victoria Groner, Catherine Fanjoy, Sita Dandiker, Kathleen Blazer, Jada G Hamilton, Kenneth Offit

{"title":"Genetics healthcare providers' experiences counseling patients with results from consumer genomic testing.","authors":"Magan Trottier, Dina Green, Hannah Ovadia, Amanda Catchings, Julia Gruberg, Victoria Groner, Catherine Fanjoy, Sita Dandiker, Kathleen Blazer, Jada G Hamilton, Kenneth Offit","doi":"10.1002/mgg3.2508","DOIUrl":"10.1002/mgg3.2508","url":null,"abstract":"Background: Consumer genomic testing (CGT), including direct-to-consumer and consumer-initiated testing, is increasingly widespread yet has limited regulatory oversight. To assess the current state, we surveyed genetics healthcare providers' experiences with CGT.Methods: A retrospective survey about experiences counseling on CGT results was completed by 139 respondents recruited from the National Society of Genetic Counselors, Clinical Cancer Genomics Community of Practice, and genetics professional societies.Results: Among respondents, 41% disagreed with the statement that potential benefits of CGT outweigh harms, 21% agreed, and 38% were undecided. A total of 94% encountered ≥1 challenge counseling CGT patients, including adverse psychosocial events (76%), incorrect variant interpretation (68%), and unconfirmed results (69%); unconfirmed results were more common among oncology providers (p = 0.03). Providers reporting higher total challenge scores (p = 0.004) or more psychosocial or interpretation challenges (p ≤ 0.01) were more likely to indicate CGT harms outweigh benefits. Those with higher CGT clinical volume were more likely to indicate benefits outweigh harms (p = 0.003). Additional CGT challenges included patient understanding and communication of results, false negatives, incorrect testing/care, and financial costs; seven respondents (6%) documented positive outcomes.Conclusion: Providers counseling CGT patients encounter psychosocial and medical challenges. Collaborations between regulators, CGT laboratories, providers, and consumers may help mitigate risks.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976174","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}

引用次数: 0

Dramatic Clinical Improvement With Biotin Mega-Dose Therapy in a Neonate With Holocarboxylase Synthetase Deficiency. 采用生物素巨剂量疗法治疗患有整体羧化酶合成酶缺乏症的新生儿，临床症状明显改善。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-08-01 DOI: 10.1002/mgg3.70002

Seon Woo Kim, Hyeon Joo Lee, Naye Choi, Ee-Kyung Kim, Jung Min Ko

{"title":"Dramatic Clinical Improvement With Biotin Mega-Dose Therapy in a Neonate With Holocarboxylase Synthetase Deficiency.","authors":"Seon Woo Kim, Hyeon Joo Lee, Naye Choi, Ee-Kyung Kim, Jung Min Ko","doi":"10.1002/mgg3.70002","DOIUrl":"10.1002/mgg3.70002","url":null,"abstract":"Introduction: Holocarboxylase synthetase deficiency (HLCS deficiency, OMIM #253270) is an exceedingly rare metabolic disorder resulting in multiple carboxylase deficiencies owing to impaired biotin cycle. Clinical manifestations include severe metabolic acidosis, hyperammonemia, tachypnea, skin rash, alopecia, feeding problems, hypotonia, developmental delay, seizures, and, in severe cases, death.Methods and results: An 8-day-old female neonate presented with severe lactic acidosis, necessitating sedation and mechanical ventilation. Despite receiving supportive care, no evident clinical improvement was observed, accompanied by the onset of generalized ichthyosis. Genetic analysis of actionable metabolic disorders revealed compound heterozygous variants of HLCS (NM_000411.8), specifically c.[710T>C (p.Leu237Pro)]; [1544G>A (p.Ser515Asn)], prompting the initiation of biotin mega-dose therapy (10 mg/day). Remarkably, dramatic clinical improvement in lactic acidosis was observed the day after initiating biotin administration, leading to the discontinuation of mechanical ventilation within 6 days. The patient remained in stable condition during follow-up, exhibiting normal growth and development along with consistently stable laboratory findings up to 18 months of age.Conclusion: Our case highlights the significance of early genetic testing in neonates with unexplained metabolic disorders to enable timely diagnosis and therapy initiation. Biotin therapy has demonstrated remarkable efficacy in improving the clinical condition of patients with HLCS deficiency, leading to favorable outcomes.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080962","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}

引用次数: 0

Hereditary breast cancer next-generation sequencing panel evaluation in the south region of Brazil: A novel BRCA2 candidate pathogenic variant is reported. 巴西南部地区遗传性乳腺癌新一代测序面板评估：报告了一种新型 BRCA2 候选致病变体。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-08-01 DOI: 10.1002/mgg3.2504

Cesar Augusto B Duarte, Carlos Alberto Dos Santos, Cristine Domingues D de Oliveira, Cleverton César Spautz, Laura Masami Sumita, Sueli Massumi Nakatani

{"title":"Hereditary breast cancer next-generation sequencing panel evaluation in the south region of Brazil: A novel BRCA2 candidate pathogenic variant is reported.","authors":"Cesar Augusto B Duarte, Carlos Alberto Dos Santos, Cristine Domingues D de Oliveira, Cleverton César Spautz, Laura Masami Sumita, Sueli Massumi Nakatani","doi":"10.1002/mgg3.2504","DOIUrl":"10.1002/mgg3.2504","url":null,"abstract":"Background: In this article, we delineate a loosely selected cohort comprising patients with a history of early-onset breast cancer and/or a familial occurrence of cancer. The aim of this study was to gain insights into the presence of breast cancer-related gene variants in a population from a micro-region in southern Brazil, specifically the Metropolitan Region of Curitiba. This area exhibits a highly genetically mixed population, mirroring the general characteristics of the Brazilian people.Methods: Comprehensive next-generation sequencing (NGS) multigene panel testing was conducted on 12 patients from the region, utilizing three different library preparation methods.Results: Two pathogenic variants and one candidate pathogenic variant were identified: BRCA2 c.8878C>T, p.Gln2960Ter; CHEK2 c.1100del, p.Thr367Metfs15, and BRCA2 c.3482dup, p.Asp1161Glufs3.Conclusion: BRCA2 c.3482dup, a novel candidate pathogenic variant, previously unpublished, is reported. The prevalence of pathogenic variants in this small cohort is similar to that described in the literature. All different library preparation methods were equally proficient in enabling the detection of these variants.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913315","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}

引用次数: 0

Developmental epileptic encephalopathy caused by homozygosity of a c.172+1G>C variant in the WWOX gene. WWOX基因中c.172+1G>C变异的同源性导致的发育性癫痫脑病。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-08-01 DOI: 10.1002/mgg3.2500

Yang You, Wenjuan Wu, Yakun Du, Jintong Hu, Baoguang Li

{"title":"Developmental epileptic encephalopathy caused by homozygosity of a c.172+1G>C variant in the WWOX gene.","authors":"Yang You, Wenjuan Wu, Yakun Du, Jintong Hu, Baoguang Li","doi":"10.1002/mgg3.2500","DOIUrl":"10.1002/mgg3.2500","url":null,"abstract":"Background: Variations in the WWOX gene have been identified as the leading cause of several central nervous system disorders. However, most previous reports have focused on the description of clinical phenotype, neglecting functional verification. Herein, we presented a case of a patient with developmental epileptic encephalopathy (DEE) caused by WWOX gene variation.Case presentation: Our patient was a 13-month-old girl with abnormal facial features, including facial hypotonia, arched eyebrows, a broad nose, and a depressed nasal bridge. She also had sparse and yellow hair, a low anterior hairline, and a short neck. Before the age of 8 months, she was suffering from mild seizures. Her developmental delay gradually worsened, and she suffered infantile spasms. After treatment with vigabatrin, seizures subsided. WWOX gene homozygous variation c.172+1G>C was identified using whole exome sequencing. Further minigene assay confirmed that the variation site affected splicing, causing protein truncation and affecting its function.Conclusion: Clinical phenotype and minigene results suggest that WWOX gene homozygous variation c.172+1G>C can cause severe DEE. We also concluded that vigabatrin can effectively treat seizures.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889707","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}

引用次数: 0