Clinical Genetics最新文献_第10页

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-08-21 DOI: 10.1111/cge.14608

Marlène Malbos, Gabriella Vera, Harsh Sheth, Rhonda E. Schnur, Aurélien Juven, Anne-Claire Brehin, Jayesh Sheth, Ajit Gandhi, Faye L. Shapiro, Ange-Line Bruel, Florent Marguet, Amber Begtrup, Kristin G. Monaghan, Hana Safraou, Marie Brasseur-Daudruy, Frédéric Tran Mau-Them, Yannis Duffourd, Laurence Faivre, Christel Thauvin-Robinet, Paul J. Benke, Christophe Philippe

{"title":"SCYL2-related autosomal recessive neurodevelopmental disorders: Arthrogryposis multiplex congenita-4 and beyond?","authors":"Marlène Malbos, Gabriella Vera, Harsh Sheth, Rhonda E. Schnur, Aurélien Juven, Anne-Claire Brehin, Jayesh Sheth, Ajit Gandhi, Faye L. Shapiro, Ange-Line Bruel, Florent Marguet, Amber Begtrup, Kristin G. Monaghan, Hana Safraou, Marie Brasseur-Daudruy, Frédéric Tran Mau-Them, Yannis Duffourd, Laurence Faivre, Christel Thauvin-Robinet, Paul J. Benke, Christophe Philippe","doi":"10.1111/cge.14608","DOIUrl":"10.1111/cge.14608","url":null,"abstract":"SCY1-like protein 2 (SCYL2) is a member of the SCY1-like pseudokinase family which regulates secretory protein trafficking. It plays a crucial role in the nervous system by suppressing excitotoxicity in the developing brain. Scyl2 knockout mice have excess prenatal mortality and survivors show severe neurological dysfunction. Bi-allelic loss-of-function (LOF) variants in SCYL2 were recently associated with arthrogryposis multiplex congenita-4 (AMC4) following the report of 6 individuals from two consanguineous unrelated families. The AMC4 phenotype described included severe arthrogryposis, corpus callosum agenesis, epilepsy and frequently, early death. We describe here two additional similarly affected individuals with AMC4, including one diagnosed in the prenatal period, with bi-allelic LOF variants in SCYL2, and two individuals homozygous for missense variants in the protein kinase domain of SCYL2 and presenting with developmental delay only. Our study confirms the association of SCYL2 with AMC4 and suggests a milder phenotype can occur, extending the phenotypic spectrum of autosomal recessive SCYL2-related disorders.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 6","pages":"757-763"},"PeriodicalIF":2.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14608","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 PLEC variants associated with infantile cholestasis 与小儿胆汁淤积症相关的新型 PLEC 变体

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-08-21 DOI: 10.1111/cge.14611

Phawin Kor-anantakul, Huey-Ling Chen, Ya-Hui Chen, Chupong Ittiwut, Rungnapa Ittiwut, Nataruks Chaijitraruch, Kanya Suphapeetiporn, Voranush Chongsrisawat

引用次数: 0

Clinical characteristics, longitudinal adaptive functioning, and association with electroencephalogram activity in PPP2R5D-related neurodevelopmental disorder PPP2R5D 相关神经发育障碍的临床特征、纵向适应功能以及与脑电图活动的关联。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-08-21 DOI: 10.1111/cge.14612

Khemika K. Sudnawa, Nicolò Pini, Wenxing Li, Cara H. Kanner, Joseph Ryu, Sean Calamia, Jennifer M. Bain, Sylvie Goldman, Jacqueline Montes, Yufeng Shen, Wendy K. Chung

{"title":"Clinical characteristics, longitudinal adaptive functioning, and association with electroencephalogram activity in PPP2R5D-related neurodevelopmental disorder","authors":"Khemika K. Sudnawa, Nicolò Pini, Wenxing Li, Cara H. Kanner, Joseph Ryu, Sean Calamia, Jennifer M. Bain, Sylvie Goldman, Jacqueline Montes, Yufeng Shen, Wendy K. Chung","doi":"10.1111/cge.14612","DOIUrl":"10.1111/cge.14612","url":null,"abstract":"Protein phosphatase 2 regulatory subunit B56δ related neurodevelopmental disorder (PPP2R5D-related NDD) is largely caused by de novo heterozygous missense PPP2R5D variants. We report medical characteristics, longitudinal adaptive functioning, and in-person neurological, motor, cognitive, and electroencephalogram (EEG) activity for PPP2R5D-related NDD. Forty-two individuals (median age 6 years, range = 0.8–25.3) with pathogenic/likely pathogenic PPP2R5D variants were assessed, and almost all variants were missense (97.6%) and de novo (85.7%). Common clinical symptoms were developmental delay, hypotonia, macrocephaly, seizures, autism, behavioral challenges, and sleep problems. The mean Gross motor functional measure-66 was 60.2 ± 17.3% and the mean Revised upper limb module score was 25.9 ± 8.8. The Vineland-3 adaptive behavior composite score (VABS-3 ABC) at baseline was low (M = 61.7 ± 16.8). VABS-3 growth scale value scores increased from baseline in all subdomains (range = 0.6–5.9) after a mean follow-up of 1.3 ± 0.3 years. EEG beta and gamma power were negatively correlated with VABS-3 score; p < 0.05. Individuals had a mean Quality-of-life inventory-disability score of 74.7 ± 11.4. Twenty caregivers (80%) had a risk of burnout based on the Caregiver burden inventory. Overall, the most common clinical manifestations of PPP2R5D-related NDD were impaired cognitive, adaptive function, and motor skills; and EEG activity was associated with adaptive functioning. This clinical characterization describes the natural history in preparation for clinical trials.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"107 1","pages":"34-43"},"PeriodicalIF":2.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expanding the phenotypes of ABL1 deficiency syndromes: When mutations in different isoforms Lead to different diseases 扩展 ABL1 缺乏综合征的表型：当不同同工酶突变导致不同疾病时

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-08-18 DOI: 10.1111/cge.14609

Eliane Chouery, Cybel Mehawej, Aline Mansour, Sandra Corbani, Rima Korban, Richard Zalloum, Andre Megarbane

引用次数: 0

Active spread of β-thalassemia beyond the thalassemia belt: A study on a Russian population β地中海贫血在地中海贫血带以外积极扩散：对俄罗斯人口的研究。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-08-14 DOI: 10.1111/cge.14606

Ekaterina Shchemeleva, Valentina V. Salomashkina, Daria Selivanova, Nina Tsvetaeva, Anait Melikyan, Liliya Doronina, Vadim L. Surin

{"title":"Active spread of β-thalassemia beyond the thalassemia belt: A study on a Russian population","authors":"Ekaterina Shchemeleva, Valentina V. Salomashkina, Daria Selivanova, Nina Tsvetaeva, Anait Melikyan, Liliya Doronina, Vadim L. Surin","doi":"10.1111/cge.14606","DOIUrl":"10.1111/cge.14606","url":null,"abstract":"β-Thalassemia is a disease traditionally associated with thalassemia belt countries. Nonetheless, as global migration intensifies, β-thalassemia–causing variants spread far from their origin. We investigated this process to detect some patterns underlying its course. We analyzed β-thalassemia–causing variants and the origin of 676 unrelated participants in Moscow, the largest city of Russia, far away from the thalassemia belt. Our analyses revealed that modern Russia has one of the broadest spectra of thalassemia-causing variants: 46 different variants, including two novel β0 variants. Only a small proportion of the reported pathogenic variants likely originated in the resident subpopulation. Almost half of the variants that supposedly had emerged outside the Russian borders have already been assimilated by (were found in) the resident subpopulation. The primary modern source of immigration transferring thalassemia to a nonthalassemic part of Russia is the Caucasus region. We also found traces of ancient migration flows from non-Caucasus countries. Our data indicate that β-thalassemia–causing variants are actively spilling over into resident populations of countries outside thalassemia belt regions. Therefore, viewing thalassemia as a disease exclusive to specific ethnic groups creates a mind trap that can complicate the diagnosis.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"107 1","pages":"23-33"},"PeriodicalIF":2.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In memory of Ludwine Messiaen, Ph.D. (1956–2024) 纪念 Ludwine Messiaen 博士 (1956-2024)。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-08-14 DOI: 10.1111/cge.14598

Elfride De Baere, Eric Legius, Reiner A. Veitia, Kathleen Claes

引用次数: 0

Featured Cover 精选封面

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-08-11 DOI: 10.1111/cge.14607

Shagun Aggarwal, Venugopal Satidevi Vineeth, Shrutika S. Padwal, Sameer Ahmed Bhat, Arpita Singh, Aditya Kulkarni, Mallikarjun Patil, Karthik Tallapaka, Divya Pasumarthi, Vijayasree Venkatapuram, Pragna Lakshmi Thotakura, Ashwin Dalal, Rashna Bhandari

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The clinical and genetic spectrum of mitochondrial diseases in China: A multicenter retrospective cross-sectional study 中国线粒体疾病的临床和遗传谱：多中心回顾性横断面研究。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-08-09 DOI: 10.1111/cge.14605

Yang Zhao, Xutong Zhao, Kunqian Ji, Junling Wang, Yuying Zhao, Jie Lin, Qiang Gang, Meng Yu, Yun Yuan, Haishan Jiang, Chong Sun, Fang Fang, Chuanzhu Yan, Zhaoxia Wang

{"title":"The clinical and genetic spectrum of mitochondrial diseases in China: A multicenter retrospective cross-sectional study","authors":"Yang Zhao, Xutong Zhao, Kunqian Ji, Junling Wang, Yuying Zhao, Jie Lin, Qiang Gang, Meng Yu, Yun Yuan, Haishan Jiang, Chong Sun, Fang Fang, Chuanzhu Yan, Zhaoxia Wang","doi":"10.1111/cge.14605","DOIUrl":"10.1111/cge.14605","url":null,"abstract":"Mitochondrial diseases (MtDs) present diverse clinical phenotypes, yet large-scale studies are hindered by their rarity. This retrospective, multicenter study, conducted across five Chinese hospitals' neurology departments from 2009 to 2019, aimed to address this gap. Nationwide, 1351 patients were enrolled, with a median onset age of 14.0 (18.5) years. The predominant phenotype was mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) (45.0%). Mitochondrial DNA (mtDNA) mutations were prevalent (87.4%), with m.3243A>G being the most common locus (48.7%). Meanwhile, POLG mutations in nuclear DNA (nDNA) accounted for 16.5%. Comparative analysis based on age groups (with a cut-off at 14 years) revealed the highest prevalence of MELAS, with Leigh syndrome (LS) and chronic progressive external ophthalmoplegia (CPEO) being the second most common phenotypes in junior and senior groups, respectively. Notably, the most commonly mutated nuclear genes varied across age groups. In conclusion, MELAS predominated in this Chinese MtD cohort, underscored by m.3243A>G and POLG as principal mtDNA mutations and pathogenic nuclear genes. The phenotypic and genotypic disparities observed among different age cohorts highlight the complex nature of MtDs.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 6","pages":"733-744"},"PeriodicalIF":2.9,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14605","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 landscape of hearing loss in prelingual deaf patients of eastern Iran: Insights from exome sequencing analysis 伊朗东部语前聋患者听力损失的遗传特征：外显子组测序分析的启示

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-08-06 DOI: 10.1111/cge.14599

Masoome Alerasool, Atieh Eslahi, Barbara Vona, Mir Salar Kahaei, Nasrin Kaseb Mojaver, Mohsen Rajati, Alireza Pasdar, Mohammad Mehdi Ghasemi, Ehsan Saburi, Reza Mousavi Ardehaie, Majid Hadadi Aval, Mohammad Reza Tale, Navid Nourizadeh, Mohammad Reza Afzalzadeh, Hamid Tayarani Niknezhad, Majid Mojarrad

{"title":"Genetic landscape of hearing loss in prelingual deaf patients of eastern Iran: Insights from exome sequencing analysis","authors":"Masoome Alerasool, Atieh Eslahi, Barbara Vona, Mir Salar Kahaei, Nasrin Kaseb Mojaver, Mohsen Rajati, Alireza Pasdar, Mohammad Mehdi Ghasemi, Ehsan Saburi, Reza Mousavi Ardehaie, Majid Hadadi Aval, Mohammad Reza Tale, Navid Nourizadeh, Mohammad Reza Afzalzadeh, Hamid Tayarani Niknezhad, Majid Mojarrad","doi":"10.1111/cge.14599","DOIUrl":"10.1111/cge.14599","url":null,"abstract":"Hearing loss is one of the most prevalent genetic disorders in humans. Locus and allelic heterogeneity cause fundamental challenges in hearing loss genetic diagnosis and management of patients and their families. This study examined the genetic profile of patients with prelingual hearing loss who were referred to the Genetic Foundation of Khorasan Razavi spanning over a decade. Deleterious variants in GJB2 were evaluated through Sanger sequencing among 745 non-syndromic hearing loss patients. Furthermore, exome sequencing was applied in 250 patients with negative GJB2 sequencing results and 30 patients with syndromic hearing loss. The findings revealed a relatively low frequency of GJB2 variants among the studied patients. Exome sequencing successfully identified the genetic causes of hearing loss in 70% of the patients. Moreover, variants in 10 genes, namely SLC26A4, MYO15A, TMPRSS3, TMC1, OTOF, CDH23, PJVK, MYO7A, TECTA, and PCDH15, accounted for 66% of the positive exome sequencing findings in this study. At least three prevalent founder alleles in the hearing-impaired population of eastern Iran were identified. This study emphasizes the efficiency of exome sequencing as a powerful tool for determining the etiology of prelingual hearing loss in the eastern Iranian population.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 6","pages":"693-701"},"PeriodicalIF":2.9,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinicogenetic characterization of cerebrotendinous xanthomatosis in Brazil 巴西脑膜黄瘤病的临床遗传学特征。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-08-05 DOI: 10.1111/cge.14602

Helena Fussiger, Pedro Lucas G. S. B. Lima, Paulo V. S. Souza, Fernando Freua, Antonette S. E. Husny, Emília K. E. A. Leão, Pedro Braga-Neto, Fernando Kok, David S. Lynch, Jonas A. M. Saute, Paulo R. Nóbrega

{"title":"Clinicogenetic characterization of cerebrotendinous xanthomatosis in Brazil","authors":"Helena Fussiger, Pedro Lucas G. S. B. Lima, Paulo V. S. Souza, Fernando Freua, Antonette S. E. Husny, Emília K. E. A. Leão, Pedro Braga-Neto, Fernando Kok, David S. Lynch, Jonas A. M. Saute, Paulo R. Nóbrega","doi":"10.1111/cge.14602","DOIUrl":"10.1111/cge.14602","url":null,"abstract":"There are few cerebrotendineous xanthomatosis (CTX) case series and observational studies including a significant number of Latin American patients. We describe a multicenter Brazilian cohort of patients with CTX highlighting their clinical phenotype, recurrent variants and assessing possible genotype–phenotype correlations. We analyzed data from all patients with clinical and molecular or biochemical diagnosis of CTX regularly followed at six genetics reference centers in Brazil between March 2020 and August 2023. We evaluated 38 CTX patients from 26 families, originating from 4 different geographical regions in Brazil. Genetic analysis identified 13 variants in the CYP27A1 gene within our population, including 3 variants that had not been previously described. The most frequent initial symptom of CTX in Brazil was cataract (27%), followed by xanthomas (24%), chronic diarrhea (13.5%), and developmental delay (13.5%). We observed that the median age at loss of ambulation correlates with the age of onset of neurological symptoms, with an average interval of 10 years (interquartile range 6.9 to 11 years). This study represents the largest CTX case series ever reported in South America. We describe phenotypic characteristics and report three new pathogenic or likely pathogenic variants.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 6","pages":"721-732"},"PeriodicalIF":2.9,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0