دورية أكاديمية
Heterozygous ZNHIT3 variants within the 17q12 recurrent deletion region are associated with Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome.
| العنوان: | Heterozygous ZNHIT3 variants within the 17q12 recurrent deletion region are associated with Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome. |
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| المؤلفون: | Brakta S; Section of Reproductive Endocrine, Infertility, & Genetics, Department of Obstetrics & Gynecology, Medical College of Georgia at Augusta University, Augusta, GA, USA. Electronic address: sbrakta@augusta.edu., Du Q; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA., Chorich LP; Section of Reproductive Endocrine, Infertility, & Genetics, Department of Obstetrics & Gynecology, Medical College of Georgia at Augusta University, Augusta, GA, USA., Hawkins ZA; Section of Reproductive Endocrine, Infertility, & Genetics, Department of Obstetrics & Gynecology, Medical College of Georgia at Augusta University, Augusta, GA, USA., Sullivan ME; University of Pittsburgh, Pittsburgh, PA, USA., Ko EK; University of Pennsylvania, Philadelphia, PA, USA., Kim HG; Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ, USA., Knight J; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA; Yale Center for Genome Analysis, Yale University, New Haven, CT, USA., Taylor HS; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA., Friez M; Greenwood Genetics Center, Greenwood, SC, USA., Phillips JA 3rd; Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University, Nashville, TN, USA., Layman LC; Section of Reproductive Endocrine, Infertility, & Genetics, Department of Obstetrics & Gynecology, Medical College of Georgia at Augusta University, Augusta, GA, USA; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA; Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA, USA. |
| المصدر: | Molecular and cellular endocrinology [Mol Cell Endocrinol] 2024 Aug 01; Vol. 589, pp. 112237. Date of Electronic Publication: 2024 Apr 08. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: North Holland Publishing Country of Publication: Ireland NLM ID: 7500844 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8057 (Electronic) Linking ISSN: 03037207 NLM ISO Abbreviation: Mol Cell Endocrinol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Limerick : North Holland Publishing Original Publication: Amsterdam, North-Holland. |
| مواضيع طبية MeSH: | 46, XX Disorders of Sex Development*/genetics , Chromosomes, Human, Pair 17*/genetics , Congenital Abnormalities*/genetics , Heterozygote* , Mullerian Ducts*/abnormalities, Adolescent ; Adult ; Female ; Humans ; Pedigree |
| مستخلص: | The molecular basis of mullerian aplasia, also known as Mayer-Rokitansky-Kuster Hauser (MRKH) or congenital absence of the uterus and vagina, is largely unknown. We applied a multifaceted genetic approach to studying the pathogenesis of MRKH including exome sequencing of trios and duos, genome sequencing of families, qPCR, RT-PCR, and Sanger sequencing to detect intragenic deletions, insertions, splice variants, single nucleotide variants, and rearrangements in 132 persons with MRKH. We identified two heterozygous variants in ZNHIT3 localized to a commonly involved CNV region at chromosome 17q12 in two different families with MRKH. One is a frameshift, truncating variant that is predicted to interfere with steroid hormone binding of the LxxLL sequence of the C-terminal region. The second variant is a double missense/stopgain variant. Both variants impair protein expression in vitro. In addition, four more probands with MRKH harbored the stopgain variant without the nearby missense variant. In total, 6/132 (4.5%) of patients studied, including five with associated anomalies (type 2 MRKH), had ZNHIT3 variants that impair function in vitro. Our findings implicate ZNHIT3 as an important gene associated with MRKH within the 17q12 CNV region. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Mayer-Rokitansky-Kuster Hauser; Mullerian aplasia; Next generation sequencing; Nonsense-mediated mRNA decay; Pathogenic variants; ZNHIT3 |
| المشرفين على المادة: | 0 (ZNHIT3 protein, human) |
| SCR Disease Name: | Mullerian aplasia |
| تواريخ الأحداث: | Date Created: 20240410 Date Completed: 20240601 Latest Revision: 20240610 |
| رمز التحديث: | 20240610 |
| DOI: | 10.1016/j.mce.2024.112237 |
| PMID: | 38599276 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-8057 |
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| DOI: | 10.1016/j.mce.2024.112237 |