دورية أكاديمية
Bi-allelic POLR3A Loss-of-Function Variants Cause Autosomal-Recessive Wiedemann-Rautenstrauch Syndrome.
| العنوان: | Bi-allelic POLR3A Loss-of-Function Variants Cause Autosomal-Recessive Wiedemann-Rautenstrauch Syndrome. |
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| المؤلفون: | Wambach JA; Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA; St. Louis Children's Hospital, St. Louis, MO 63110, USA. Electronic address: wambachj@wustl.edu., Wegner DJ; Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA; St. Louis Children's Hospital, St. Louis, MO 63110, USA., Patni N; Department of Pediatrics and Center for Human Nutrition, UT Southwestern Medical Center, Dallas, TX 75390, USA., Kircher M; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA., Willing MC; Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA; St. Louis Children's Hospital, St. Louis, MO 63110, USA., Baldridge D; Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA; St. Louis Children's Hospital, St. Louis, MO 63110, USA., Xing C; McDermott Center for Human Growth and Development, Department of Bioinformatics and Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, TX 75390, USA., Agarwal AK; Division of Nutrition Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Vergano SAS; Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA 23507, USA., Patel C; Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, QLD 4029, Australia., Grange DK; Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA; St. Louis Children's Hospital, St. Louis, MO 63110, USA., Kenney A; Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA 23507, USA., Najaf T; Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA; St. Louis Children's Hospital, St. Louis, MO 63110, USA; Fetal Care Center, Washington University School of Medicine, St. Louis, MO 63110, USA., Nickerson DA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA., Bamshad MJ; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Department of Pediatrics, University of Washington, Seattle, WA 98195, USA., Cole FS; Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA; St. Louis Children's Hospital, St. Louis, MO 63110, USA., Garg A; Division of Nutrition Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: abhimanyu.garg@utsouthwestern.edu. |
| المصدر: | American journal of human genetics [Am J Hum Genet] 2018 Dec 06; Vol. 103 (6), pp. 968-975. Date of Electronic Publication: 2018 Nov 07. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 0370475 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1537-6605 (Electronic) Linking ISSN: 00029297 NLM ISO Abbreviation: Am J Hum Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2008- : [Cambridge, MA] : Cell Press Original Publication: Baltimore, American Society of Human Genetics. |
| مواضيع طبية MeSH: | Fetal Growth Retardation/*genetics , Genetic Variation/*genetics , Loss of Heterozygosity/*genetics , Progeria/*genetics , RNA Polymerase III/*genetics, Adolescent ; Adult ; Alleles ; Child, Preschool ; Female ; Genotype ; Humans ; Phenotype ; Young Adult |
| مستخلص: | Wiedemann-Rautenstrauch syndrome (WRS), also known as neonatal progeroid syndrome, is a rare disorder of unknown etiology. It has been proposed to be autosomal-recessive and is characterized by variable clinical features, such as intrauterine growth restriction and poor postnatal weight gain, characteristic facial features (triangular appearance to the face, convex nasal profile or pinched nose, and small mouth), widened fontanelles, pseudohydrocephalus, prominent scalp veins, lipodystrophy, and teeth abnormalities. A previous report described a single WRS patient with bi-allelic truncating and splicing variants in POLR3A. Here we present seven additional infants, children, and adults with WRS and bi-allelic truncating and/or splicing variants in POLR3A. POLR3A, the largest subunit of RNA polymerase III, is a DNA-directed RNA polymerase that transcribes many small noncoding RNAs that regulate transcription, RNA processing, and translation. Bi-allelic missense variants in POLR3A have been associated with phenotypes distinct from WRS: hypogonadotropic hypogonadism and hypomyelinating leukodystrophy with or without oligodontia. Our findings confirm the association of bi-allelic POLR3A variants with WRS, expand the clinical phenotype of WRS, and suggest specific POLR3A genotypes associated with WRS and hypomyelinating leukodystrophy. (Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.) |
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| معلومات مُعتمدة: | U54 HG006493 United States HG NHGRI NIH HHS; R21 HL120760 United States HL NHLBI NIH HHS; K12 HL120002 United States HL NHLBI NIH HHS; UM1 HG006493 United States HG NHGRI NIH HHS; R01 DK105448 United States DK NIDDK NIH HHS; UL1 TR001105 United States TR NCATS NIH HHS; R01 HL065174 United States HL NHLBI NIH HHS; UL1 RR024982 United States RR NCRR NIH HHS; K08 HL105891 United States HL NHLBI NIH HHS; R33 HL120760 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: POLR3A, RNA polymerase 3A; Wiedemann-Rautenstrauch syndrome; neonatal progeroid syndrome |
| المشرفين على المادة: | EC 2.7.7.6 (POLR3A protein, human) EC 2.7.7.6 (RNA Polymerase III) |
| SCR Disease Name: | Progeroid syndrome, neonatal |
| تواريخ الأحداث: | Date Created: 20181112 Date Completed: 20190514 Latest Revision: 20240405 |
| رمز التحديث: | 20240405 |
| مُعرف محوري في PubMed: | PMC6288318 |
| DOI: | 10.1016/j.ajhg.2018.10.010 |
| PMID: | 30414627 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1537-6605 |
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| DOI: | 10.1016/j.ajhg.2018.10.010 |