Heterozygous ZNHIT3 variants within the 17q12 recurrent deletion region are associated with Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome.
In: Molecular and cellular endocrinology, Jg. 589 (2024-08-01), S. 112237
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Zugriff:
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.)
Titel: |
Heterozygous ZNHIT3 variants within the 17q12 recurrent deletion region are associated with Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome.
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Autor/in / Beteiligte Person: | Brakta, S ; Du, Q ; Chorich, LP ; Hawkins, ZA ; Sullivan, ME ; Ko, EK ; Kim, HG ; Knight, J ; Taylor, HS ; Friez, M ; Phillips JA 3rd ; Layman, LC |
Zeitschrift: | Molecular and cellular endocrinology, Jg. 589 (2024-08-01), S. 112237 |
Veröffentlichung: | Limerick : North Holland Publishing ; <i>Original Publication</i>: Amsterdam, North-Holland., 2024 |
Medientyp: | academicJournal |
ISSN: | 1872-8057 (electronic) |
DOI: | 10.1016/j.mce.2024.112237 |
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