دورية أكاديمية
Non-Invasive Detection of a De Novo Frameshift Variant of STAG2 in a Female Fetus: Escape Genes Influence the Manifestation of X-Linked Diseases in Females
| العنوان: | Non-Invasive Detection of a De Novo Frameshift Variant of STAG2 in a Female Fetus: Escape Genes Influence the Manifestation of X-Linked Diseases in Females |
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| المؤلفون: | Provenzano, Aldesia, La Barbera, Andrea, Lai, Francesco, Perra, Andrea, Farina, Antonio, Cariati, Ettore, Zuffardi, Orsetta, Giglio, Sabrina |
| المساهمون: | Provenzano, Aldesia, La Barbera, Andrea, Lai, Francesco, Perra, Andrea, Farina, Antonio, Cariati, Ettore, Zuffardi, Orsetta, Giglio, Sabrina |
| سنة النشر: | 2022 |
| المجموعة: | Università degli Studi di Cagliari: UNICA IRIS |
| مصطلحات موضوعية: | X-linked disease, non-invasive whole exome sequencing, fetal cell-free DNA, escapee gene, X-inactivation, Mullegama–Klein–Martinez syndrome (MKMS), STAG2 gene |
| الوصف: | Background: We report on a 20-week-old female fetus with a diaphragmatic hernia and other malformations, all of which appeared after the first-trimester ultrasound. Methods and Results: Whole trio exome sequencing (WES) on cell-free fetal DNA (cff-DNA) revealed a de novo frameshift variant of the X-linked STAG2 gene. Loss-of-function (LoF) STAG2 variants cause either holoprosencephaly (HPE) or Mullegama–Klein–Martinez syndrome (MKMS), are de novo, and only affect females, indicating male lethality. In contrast, missense mutations associate with milder forms of MKMS and follow the classic X-linked recessive inheritance transmitted from healthy mothers to male offspring. STAG2 has been reported to escape X-inactivation, suggesting that disease onset in LoF females is dependent on inadequate dosing for at least some of the transcripts, as is the case with a part of the autosomal dominant diseases. Missense STAG2 variants produce a quantity of transcripts, which, while resulting in a different protein, leads to disease only in hemizygous males. Similar inheritance patterns are described for other escapee genes. Conclusions: This study confirms the advantage of WES on cff-DNA and emphasizes the role of the type of the variant in X-linked disorders. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35887945; info:eu-repo/semantics/altIdentifier/wos/WOS:000831365000001; volume:11; issue:14; numberofpages:10; journal:JOURNAL OF CLINICAL MEDICINE; http://hdl.handle.net/11584/342080Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85136356779; https://www.mdpi.com/2077-0383/11/14/4182Test |
| DOI: | 10.3390/jcm11144182 |
| الإتاحة: | https://doi.org/10.3390/jcm11144182Test http://hdl.handle.net/11584/342080Test https://www.mdpi.com/2077-0383/11/14/4182Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.DD0F694B |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/jcm11144182 |
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