دورية أكاديمية
AHDC1 missense mutations in Xia-Gibbs syndrome.
| العنوان: | AHDC1 missense mutations in Xia-Gibbs syndrome. |
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| المؤلفون: | Khayat MM; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.; These authors contributed equally to this work., Hu J; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.; These authors contributed equally to this work., Jiang Y; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.; These authors contributed equally to this work., Li H; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA., Chander V; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., Dawood M; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA., Hansen AW; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., Li S; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA., Friedman J; UCSD Departments of Neuroscience and Pediatrics, Rady Children's Hospital Division of Neurology, Rady Children's Institute for Genomic Medicine, San Diego, CA, USA., Cross L; Department of Pediatrics and Genetics, Children's Mercy Hospitals, Kansas City, MO, USA., Bijlsma EK; Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands., Ruivenkamp CAL; Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands., Sansbury FH; All Wales Medical Genomics Service, NHS Wales Cardiff and Vale University Health Board, Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK., Innis JW; Departments of Human Genetics, Pediatrics, and Internal Medicine, University of Michigan, Ann Arbor, MI, USA., O'Shea JO; Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA., Meng Q; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA., Rosenfeld JA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., McWalter K; GeneDx, Gaithersburg, MD, USA., Wangler MF; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Neurological Research Institute, Houston, TX, USA., Lupski JR; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Posey JE; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., Murdock D; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., Gibbs RA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. |
| المصدر: | HGG advances [HGG Adv] 2021 Oct 14; Vol. 2 (4). Date of Electronic Publication: 2021 Aug 10. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc Country of Publication: United States NLM ID: 101772885 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-2477 (Electronic) Linking ISSN: 26662477 NLM ISO Abbreviation: HGG Adv Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: New York : Elsevier Inc., [2020]- |
| مستخلص: | Xia-Gibbs syndrome (XGS; MIM: 615829) is a phenotypically heterogeneous neurodevelopmental disorder (NDD) caused by newly arising mutations in the AT-Hook DNA-Binding Motif-Containing 1 ( AHDC1 ) gene that are predicted to lead to truncated AHDC1 protein synthesis. More than 270 individuals have been diagnosed with XGS worldwide. Despite the absence of an independent assay for AHDC1 protein function to corroborate potential functional consequences of rare variant genetic findings, there are also reports of individuals with XGS-like trait manifestations who have de novo missense AHDC1 mutations and who have been provided a molecular diagnosis of the disorder. To investigate a potential contribution of missense mutations to XGS, we mapped the missense mutations from 10 such individuals to the AHDC1 conserved protein domain structure and detailed the observed phenotypes. Five newly identified individuals were ascertained from a local XGS Registry, and an additional five were taken from external reports or databases, including one publication. Where clinical data were available, individuals with missense mutations all displayed phenotypes consistent with those observed in individuals with AHDC1 truncating mutations, including delayed motor milestones, intellectual disability (ID), hypotonia, and speech delay. A subset of the 10 reported missense mutations cluster in two regions of the AHDC1 protein with known conserved domains, likely representing functional motifs. Variants outside the clustered regions score lower for computational prediction of their likely damaging effects. Overall, de novo missense variants in AHDC1 are likely diagnostic of XGS when in silico analysis of their position relative to conserved regions is considered together with disease trait manifestations. Competing Interests: Declaration of interests J.R.L. has stock ownership in 23andMe, is a paid consultant for the Regeneron Genetics Center, and is a coinventor on multiple US and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the chromosomal microarray analysis (CMA) and clinical exome sequencing (cES) offered in the Baylor Genetics (BG) Laboratory. J.R.L. serves on the Scientific Advisory Board of BG. J.F.’s spouse is Founder and Principal of Friedman Bioventure, which holds a variety of publicly traded and private biotechnology interests. K.M. is an employee of GeneDx, Inc. All other authors declare no competing interests. |
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| معلومات مُعتمدة: | UM1 HG006542 United States HG NHGRI NIH HHS; R35 NS105078 United States NS NINDS NIH HHS; K08 HG008986 United States HG NHGRI NIH HHS; T15 LM007093 United States LM NLM NIH HHS; United Kingdom WT_ Wellcome Trust; UM1 HG008898 United States HG NHGRI NIH HHS; U01 HG011758 United States HG NHGRI NIH HHS |
| تواريخ الأحداث: | Date Created: 20211224 Latest Revision: 20240222 |
| رمز التحديث: | 20240222 |
| مُعرف محوري في PubMed: | PMC8694554 |
| DOI: | 10.1016/j.xhgg.2021.100049 |
| PMID: | 34950897 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 2666-2477 |
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| DOI: | 10.1016/j.xhgg.2021.100049 |