Human Mutation最新文献_第8页

A recurrent single-exon deletion in TBCK might be under-recognized in patients with infantile hypotonia and psychomotor delay. 在婴儿期张力低下和精神运动迟缓的患者中，TBCK的复发性单外显子缺失可能未被充分认识。

IF 3.9 2区医学

Human Mutation Pub Date : 2022-12-01 Epub Date: 2022-11-06 DOI: 10.1002/humu.24497

Hongzheng Dai, Wenmiao Zhu, Bo Yuan, Nicole Walley, Kelly Schoch, Yong-Hui Jiang, John A Phillips, Melissa S Jones, Pengfei Liu, David R Murdock, Lindsay C Burrage, Brendan Lee, Jill A Rosenfeld, Rui Xiao

{"title":"A recurrent single-exon deletion in TBCK might be under-recognized in patients with infantile hypotonia and psychomotor delay.","authors":"Hongzheng Dai, Wenmiao Zhu, Bo Yuan, Nicole Walley, Kelly Schoch, Yong-Hui Jiang, John A Phillips, Melissa S Jones, Pengfei Liu, David R Murdock, Lindsay C Burrage, Brendan Lee, Jill A Rosenfeld, Rui Xiao","doi":"10.1002/humu.24497","DOIUrl":"10.1002/humu.24497","url":null,"abstract":"Advanced bioinformatics algorithms allow detection of multiple-exon copy-number variations (CNVs) from exome sequencing (ES) data, while detection of single-exon CNVs remains challenging. A retrospective review of Baylor Genetics' clinical ES patient cohort identified four individuals with homozygous single-exon deletions of TBCK (exon 23, NM_001163435.2), a gene associated with an autosomal recessive neurodevelopmental phenotype. To evaluate the prevalence of this deletion and its contribution to disease, we retrospectively analyzed single nucleotide polymorphism (SNP) array data for 8194 individuals undergoing ES, followed by PCR confirmation and RT-PCR on individuals carrying homozygous or heterozygous exon 23 TBCK deletions. A fifth individual was diagnosed with the TBCK-related disorder due to a heterozygous exon 23 deletion in trans with a c.1860+1G>A (NM_001163435.2) pathogenic variant, and three additional heterozygous carriers were identified. Affected individuals and carriers were from diverse ethnicities including European Caucasian, South Asian, Middle Eastern, Hispanic American and African American, with only one family reporting consanguinity. RT-PCR revealed two out-of-frame transcripts related to the exon 23 deletion. Our results highlight the importance of identifying single-exon deletions in clinical ES, especially for genes carrying recurrent deletions. For patients with early-onset hypotonia and psychomotor delay, this single-exon TBCK deletion might be under-recognized due to technical limitations of ES.","PeriodicalId":13061,"journal":{"name":"Human Mutation","volume":"43 12","pages":"1816-1823"},"PeriodicalIF":3.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10556276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

AutoCaSc: Prioritizing candidate genes for neurodevelopmental disorders. AutoCaSc:优选神经发育障碍的候选基因。

IF 3.9 2区医学

Human Mutation Pub Date : 2022-12-01 DOI: 10.1002/humu.24451

Johann Kaspar Lieberwirth, Benjamin Büttner, Chiara Klöckner, Konrad Platzer, Bernt Popp, Rami Abou Jamra

{"title":"AutoCaSc: Prioritizing candidate genes for neurodevelopmental disorders.","authors":"Johann Kaspar Lieberwirth, Benjamin Büttner, Chiara Klöckner, Konrad Platzer, Bernt Popp, Rami Abou Jamra","doi":"10.1002/humu.24451","DOIUrl":"https://doi.org/10.1002/humu.24451","url":null,"abstract":"Routine exome sequencing (ES) in individuals with neurodevelopmental disorders (NDD) remains inconclusive in >50% of the cases. Research analysis of unsolved cases can identify novel candidate genes but is time-consuming, subjective, and hard to compare between labs. The field, therefore, requires automated and standardized assessment methods to prioritize candidates for matchmaking. We developed AutoCaSc (https://autocasc.uni-leipzig.de) based on our candidate scoring scheme. We validated our approach using synthetic trios and real in-house trio ES data. AutoCaSc consistently (94.5% of all cases) scored the relevant variants in valid novel NDD genes in the top three ranks. In 93 real trio exomes, AutoCaSc identified most (97.5%) previously manually scored variants while evaluating additional high-scoring variants missed in manual evaluation. It identified candidate variants in previously undescribed NDD candidate genes (CNTN2, DLGAP1, SMURF1, NRXN3, and PRICKLE1). AutoCaSc enables anybody to quickly screen a variant for its plausibility in NDD. After contributing >40 descriptions of NDD-associated genes, we provide usage recommendations based on our extensive experience. Our implementation is capable of pipeline integration and therefore allows the screening of large cohorts for candidate genes. AutoCaSc empowers even small labs to a standardized matchmaking collaboration and to contribute to the ongoing identification of novel NDD entities.","PeriodicalId":13061,"journal":{"name":"Human Mutation","volume":"43 12","pages":"1795-1807"},"PeriodicalIF":3.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10562862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 6

Functional characterization of a novel TP53RK mutation identified in a family with Galloway-Mowat syndrome. 在加洛韦-莫瓦特综合征家族中发现的一种新型TP53RK突变的功能特征

IF 3.9 2区医学

Human Mutation Pub Date : 2022-12-01 DOI: 10.1002/humu.24472

Ernestine Treimer, Tugba Kalayci, Sven Schumann, Ilknur Suer, Sara Greco, Denny Schanze, Michael J Schmeisser, Susanne J Kühl, Martin Zenker

{"title":"Functional characterization of a novel TP53RK mutation identified in a family with Galloway-Mowat syndrome.","authors":"Ernestine Treimer, Tugba Kalayci, Sven Schumann, Ilknur Suer, Sara Greco, Denny Schanze, Michael J Schmeisser, Susanne J Kühl, Martin Zenker","doi":"10.1002/humu.24472","DOIUrl":"https://doi.org/10.1002/humu.24472","url":null,"abstract":"Galloway-Mowat syndrome (GAMOS) is a very rare condition characterized by early-onset nephrotic syndrome and microcephaly with variable neurologic features. While considerable genetic heterogeneity of GAMOS has been identified, the majority of cases are caused by pathogenic variants in genes encoding the four components of the Kinase, endopeptidase, and other proteins of small size (KEOPS) complex, one of which is TP53RK. Here we describe a 3-year-old male with progressive microcephaly, neurodevelopmental deficits, and glomerular proteinuria. He was found to carry a novel homozygous TP53RK missense variant, c.163C>G (p.Arg55Gly), which was considered as potentially disease-causing. We generated a morpholino tp53rk knockdown model in Xenopus laevis showing that the depletion of endogenous Tp53rk caused abnormal eye and head development. This phenotype could be rescued by the expression of human wildtype TP53RK but not by the c.163C>G mutant nor by another previously described GAMOS-associated mutant c.125G>A (p.Gly42Asp). These findings support the pathogenic role of the novel TP53RK variant.","PeriodicalId":13061,"journal":{"name":"Human Mutation","volume":"43 12","pages":"1866-1871"},"PeriodicalIF":3.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10825862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 4

Cancer-causing MAP2K1 mutation in a mosaic patient with cardio-facio-cutaneous syndrome and immunodeficiency. 心-面-皮综合征和免疫缺陷马赛克患者的致癌MAP2K1突变

IF 3.9 2区医学

Human Mutation Pub Date : 2022-12-01 DOI: 10.1002/humu.24463

Victorya Zakharova, Elena Raykina, Irina Mersiyanova, Ekaterina Deordieva, Dmitry Pershin, Victorya Vedmedskia, Yulia Rodina, Natalia Kuzmenko, Michael Maschan, Anna Shcherbina

引用次数: 0

Multiple endocrine neoplasia type 2 (MEN2) and RET specific modifications of the ACMG/AMP variant classification guidelines and impact on the MEN2 RET database. 2型多发性内分泌瘤(MEN2)和RET特异性修改ACMG/AMP变异分类指南及对MEN2 RET数据库的影响

IF 3.9 2区医学

Human Mutation Pub Date : 2022-12-01 DOI: 10.1002/humu.24486

Rebecca L Margraf, Rachel Z Alexander, Makenzie L Fulmer, Christine E Miller, Elena Coupal, Rong Mao

{"title":"Multiple endocrine neoplasia type 2 (MEN2) and RET specific modifications of the ACMG/AMP variant classification guidelines and impact on the MEN2 RET database.","authors":"Rebecca L Margraf, Rachel Z Alexander, Makenzie L Fulmer, Christine E Miller, Elena Coupal, Rong Mao","doi":"10.1002/humu.24486","DOIUrl":"https://doi.org/10.1002/humu.24486","url":null,"abstract":"The Multiple Endocrine Neoplasia type 2 (MEN2) RET proto-oncogene database, originally published in 2008, is a comprehensive repository of all publicly available RET gene variations associated with MEN2 syndromes. The variant-specific genotype/phenotype information, age of earliest reported medullary thyroid carcinoma (MTC) onset, and relevant references with a brief summary of findings are cataloged. The ACMG/AMP 2015 consensus statement on variant classification was modified specifically for MEN2 syndromes and RET variants using ClinGen sequence variant interpretation working group recommendations and ClinGen expert panel manuscripts, as well as manuscripts from the American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma and other MEN2 RET literature. The classifications for the 166 single unique variants in the MEN2 RET database were reanalyzed using the MEN2 RET specifically modified ACMG/AMP classification guidelines (version 1). Applying these guidelines added two new variant classifications to the database (likely benign and likely pathogenic) and resulted in clinically significant classification changes (e.g., from pathogenic to uncertain) in 15.7% (26/166) of the original variants. Of those clinically significant changes, the highest percentage of changes, 46.2% (12/26), were changes from uncertain to benign or likely benign. The modified ACMG/AMP criteria with MEN2 RET specifications will optimize and standardize RET variant classifications.","PeriodicalId":13061,"journal":{"name":"Human Mutation","volume":"43 12","pages":"1780-1794"},"PeriodicalIF":3.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10558942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 2

Characterization of a possible founder synonymous variant in TECTA in multiple individuals with autosomal recessive hearing loss. 多例常染色体隐性听力损失患者中TECTA可能的奠基人同义变异的特征。

IF 3.9 2区医学

Human Mutation Pub Date : 2022-12-01 DOI: 10.1002/humu.24443

Robert Chen, Maria Alejandra Diaz-Miranda, Erfan Aref-Eshghi, Tiffiney R Hartman, Christopher Griffith, Jennifer L Morrison, Patricia G Wheeler, Erin Torti, Gabriele Richard, Margaret Kenna, Elizabeth T Dechene, Nancy B Spinner, Renkui Bai, Laura K Conlin, Ian D Krantz, Sami S Amr, Minjie Luo

{"title":"Characterization of a possible founder synonymous variant in TECTA in multiple individuals with autosomal recessive hearing loss.","authors":"Robert Chen, Maria Alejandra Diaz-Miranda, Erfan Aref-Eshghi, Tiffiney R Hartman, Christopher Griffith, Jennifer L Morrison, Patricia G Wheeler, Erin Torti, Gabriele Richard, Margaret Kenna, Elizabeth T Dechene, Nancy B Spinner, Renkui Bai, Laura K Conlin, Ian D Krantz, Sami S Amr, Minjie Luo","doi":"10.1002/humu.24443","DOIUrl":"https://doi.org/10.1002/humu.24443","url":null,"abstract":"Synonymous variants have been shown to alter the correct splicing of pre-mRNAs and generate disease-causing transcripts. These variants are not an uncommon etiology of genetic disease; however, they are frequently overlooked during genetic testing in the absence of functional and clinical data. Here, we describe the occurrence of a synonymous variant [NM_005422.4 (TECTA):c.327C>T, p.(Gly109=)] in seven individuals with hearing loss from six unrelated families. The variant is not located near exonic/intronic boundaries but is predicted to impact splicing by activating a cryptic splicing donor site in exon 4 of TECTA. In vitro minigene assays show that the variant disrupts the reading frame of the canonical transcript, which is predicted to cause a premature termination codon 48 amino acids downstream of the variant, leading to nonsense-mediated decay. The variant is present in population databases, predominantly in Latinos of African ancestry, but is rare in other ethnic groups. Our findings suggest that this synonymous variant is likely pathogenic for TECTA-associated autosomal recessive hearing loss and seems to have arisen as a founder variant in this specific Latino subpopulation. This study demonstrates that synonymous variants need careful splicing assessment and support from additional testing methodologies to determine their clinical impact.","PeriodicalId":13061,"journal":{"name":"Human Mutation","volume":"43 12","pages":"1837-1843"},"PeriodicalIF":3.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9106874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 1

Mutation update: The spectra of PLEC sequence variants and related plectinopathies. 突变更新:PLEC序列变异谱和相关的凝集菌病。

IF 3.9 2区医学

Human Mutation Pub Date : 2022-12-01 Epub Date: 2022-07-29 DOI: 10.1002/humu.24434

Hassan Vahidnezhad, Leila Youssefian, Nailah Harvey, Ali Reza Tavasoli, Amir Hossein Saeidian, Soheila Sotoudeh, Aida Varghaei, Hamidreza Mahmoudi, Parvin Mansouri, Nikoo Mozafari, Omid Zargari, Sirous Zeinali, Jouni Uitto

{"title":"Mutation update: The spectra of PLEC sequence variants and related plectinopathies.","authors":"Hassan Vahidnezhad, Leila Youssefian, Nailah Harvey, Ali Reza Tavasoli, Amir Hossein Saeidian, Soheila Sotoudeh, Aida Varghaei, Hamidreza Mahmoudi, Parvin Mansouri, Nikoo Mozafari, Omid Zargari, Sirous Zeinali, Jouni Uitto","doi":"10.1002/humu.24434","DOIUrl":"10.1002/humu.24434","url":null,"abstract":"Plectin, encoded by PLEC, is a cytoskeletal linker of intermediate filaments expressed in many cell types. Plectin consists of three main domains that determine its functionality: the N-terminal domain, the Rod domain, and the C-terminal domain. Molecular defects of PLEC correlating with the functional aspects lead to a group of rare heritable disorders, plectinopathies. These multisystem disorders include an autosomal dominant form of epidermolysis bullosa simplex (EBS-Ogna), limb-girdle muscular dystrophy (LGMD), aplasia cutis congenita (ACC), and an autosomal recessive form of EBS, which may associate with muscular dystrophy (EBS-MD), pyloric atresia (EBS-PA), and/or congenital myasthenic syndrome (EBS-MyS). In this study, genotyping of over 600 Iranian patients with epidermolysis bullosa by next-generation sequencing identified 15 patients with disease-causing PLEC variants. This mutation update analyzes the clinical spectrum of PLEC in our cohort and in the literature and demonstrates the relationship between PLEC genotype and phenotypic manifestations. This study has integrated our seven novel PLEC variants and phenotypic findings with previously published data totaling 116 variants to provide the most complete overview of pathogenic PLEC variants and related disorders.","PeriodicalId":13061,"journal":{"name":"Human Mutation","volume":"43 12","pages":"1706-1731"},"PeriodicalIF":3.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10555043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 3

VariantAlert: A web-based tool to notify updates in genetic variant annotations. VariantAlert:一个基于网络的工具，用于通知遗传变异注释的更新。

IF 3.9 2区医学

Human Mutation Pub Date : 2022-12-01 DOI: 10.1002/humu.24495

Rossano Atzeni, Matteo Massidda, Giorgio Fotia, Paolo Uva

{"title":"VariantAlert: A web-based tool to notify updates in genetic variant annotations.","authors":"Rossano Atzeni, Matteo Massidda, Giorgio Fotia, Paolo Uva","doi":"10.1002/humu.24495","DOIUrl":"https://doi.org/10.1002/humu.24495","url":null,"abstract":"The reinterpretation of variants based on updated annotations is part of the routine work of research laboratories: the more data is collected about a specific variant, the higher the probability to reinterpret its classification. To support this task, we developed VariantAlert, a web-based tool to help researchers and clinicians to be constantly informed about changes in variant annotations extracted from multiple sources. VariantAlert provides daily re-annotation of variants using external resources accessed through application programming interface, such as MyVariant.info providing in turn links to gnomAD, catalogue of somatic mutations In cancer (COSMIC), ClinVar, CIViC, and many others. Researchers and clinicians can submit one or more lists of variants. If a change is detected for the annotation of a variant due to the upgrade of the underlying resource (e.g., change in gnomAD allele frequency, presence in COSMIC database, change in ClinVar classification) the user is notified by email and updated annotations are stored on the web-site. VariantAlert is freely available at https://github.com/next-crs4/VariantAlert. Installation and deployment are easy thanks to the use of the Docker platform. A Makefile allows you to easily bootstrap VariantAlert. VariantAlert is also available as a web service at https://variant-alert.crs4.it/.","PeriodicalId":13061,"journal":{"name":"Human Mutation","volume":"43 12","pages":"1808-1815"},"PeriodicalIF":3.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9b/1c/HUMU-43-1808.PMC10091775.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9297375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 1

Clinical and pathophysiological delineation of musculocontractural Ehlers-Danlos syndrome caused by dermatan sulfate epimerase deficiency (mcEDS-DSE): A detailed and comprehensive glycobiological and pathological investigation in a novel patient. 由皮肤硫酸酯epimase缺乏症(mcEDS-DSE)引起的肌肉收缩性ehers - danlos综合征的临床和病理生理描述:对一位新患者进行了详细而全面的糖生物学和病理研究。

IF 3.9 2区医学

Human Mutation Pub Date : 2022-12-01 DOI: 10.1002/humu.24437

Mari Minatogawa, Takuya Hirose, Shuji Mizumoto, Tomomi Yamaguchi, Chiai Nagae, Masashi Taki, Shuhei Yamada, Takafumi Watanabe, Tomoki Kosho

{"title":"Clinical and pathophysiological delineation of musculocontractural Ehlers-Danlos syndrome caused by dermatan sulfate epimerase deficiency (mcEDS-DSE): A detailed and comprehensive glycobiological and pathological investigation in a novel patient.","authors":"Mari Minatogawa, Takuya Hirose, Shuji Mizumoto, Tomomi Yamaguchi, Chiai Nagae, Masashi Taki, Shuhei Yamada, Takafumi Watanabe, Tomoki Kosho","doi":"10.1002/humu.24437","DOIUrl":"https://doi.org/10.1002/humu.24437","url":null,"abstract":"Musculocontractural Ehlers-Danlos syndrome caused by dermatan sulfate epimerase deficiency (mcEDS-DSE) is a rare connective tissue disorder. This is the first report describing the detailed and comprehensive clinical and pathophysiological features of mcEDS-DSE. The patient, with a novel homozygous nonsense variant (NM_013352.4:c.2601C>A:p.(Tyr867*)), exhibited mild skin hyperextensibility without fragility and small joint hypermobility, but developed recurrent large subcutaneous hematomas. Dermatan sulfate (DS) moieties on chondroitin sulfate/DS proteoglycans were significantly decreased, but remained present, in skin fibroblasts. Electron microscopy examination of skin specimens, including cupromeronic blue-staining to visualize glycosaminoglycan (GAG) chains, revealed coexistence of normally assembled collagen fibrils with attached curved GAG chains and dispersed collagen fibrils with linear GAG chains from attached collagen fibrils across interfibrillar spaces to adjacent fibrils. Residual activity of DS-epi1, encoded by DSE, and/or compensation by DS-epi2, a minor homolog of DS-epi1, may contribute to the mild skin involvement through this \"mosaic\" pattern of collagen fibril assembly.","PeriodicalId":13061,"journal":{"name":"Human Mutation","volume":"43 12","pages":"1829-1836"},"PeriodicalIF":3.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10610896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 4

De novo putative loss-of-function variants in TAF4 are associated with a neuro-developmental disorder. TAF4中新的推测功能丧失变异与神经发育障碍有关。

IF 3.9 2区医学

Human Mutation Pub Date : 2022-12-01 DOI: 10.1002/humu.24444

Beau D E Janssen, Marie-Jose H van den Boogaard, Klaske Lichtenbelt, Eleanor G Seaby, Karen Stals, Sian Ellard, Ruth Newbury-Ecob, Abhijit Dixit, Laura Roht, Sander Pajusalu, Katrin Õunap, Helen V Firth, Michael Buckley, Meredith Wilson, Tony Roscioli, Timothy Tidwell, Rong Mao, Sarah Ennis, Sjoerd J Holwerda, Koen van Gassen, Richard H van Jaarsveld

{"title":"De novo putative loss-of-function variants in TAF4 are associated with a neuro-developmental disorder.","authors":"Beau D E Janssen, Marie-Jose H van den Boogaard, Klaske Lichtenbelt, Eleanor G Seaby, Karen Stals, Sian Ellard, Ruth Newbury-Ecob, Abhijit Dixit, Laura Roht, Sander Pajusalu, Katrin Õunap, Helen V Firth, Michael Buckley, Meredith Wilson, Tony Roscioli, Timothy Tidwell, Rong Mao, Sarah Ennis, Sjoerd J Holwerda, Koen van Gassen, Richard H van Jaarsveld","doi":"10.1002/humu.24444","DOIUrl":"https://doi.org/10.1002/humu.24444","url":null,"abstract":"TATA-binding protein associated factor 4 (TAF4) is a subunit of the Transcription Factor IID (TFIID) complex, a central player in transcription initiation. Other members of this multimeric complex have been implicated previously as monogenic disease genes in human developmental disorders. TAF4 has not been described to date as a monogenic disease gene. We here present a cohort of eight individuals, each carrying de novo putative loss-of-function (pLoF) variants in TAF4 and expressing phenotypes consistent with a neuro-developmental disorder (NDD). Common features include intellectual disability, abnormal behavior, and facial dysmorphisms. We propose TAF4 as a novel dominant disease gene for NDD, and coin this novel disorder \"TAF4-related NDD\" (T4NDD). We place T4NDD in the context of other disorders related to TFIID subunits, revealing shared features of T4NDD with other TAF-opathies.","PeriodicalId":13061,"journal":{"name":"Human Mutation","volume":"43 12","pages":"1844-1851"},"PeriodicalIF":3.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/6f/HUMU-43-1844.PMC10087332.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9278849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 2