Delineation of Clinical Manifestations of the Inherited Xq24 Microdeletion Segregating with sXCI in Mothers: Two Novel Cases with Distinct Phenotypes Ranging from UBE2A Deficiency Syndrome to Recurrent Pregnancy Loss
| Autor: | Larisa I. Minaycheva, Maria E. Lopatkina, Olga A. Salyukova, Nikolay A. Skryabin, Victor S. Tarabykin, Igor N. Lebedev, Elizaveta A. Fonova, E. A. Sazhenova, Elena O. Belyaeva, Lyudmila P. Nazarenko, T. V. Nikitina, E. N. Tolmacheva, A. A. Kashevarova |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Abortion Habitual Mothers Biology X-inactivation Epigenesis Genetic 03 medical and health sciences Young Adult Pleiotropy X Chromosome Inactivation Intellectual Disability Intellectual disability Genetics medicine Humans Family history Molecular Biology Skewed X-inactivation Genetics (clinical) 030304 developmental biology 0303 health sciences Pregnancy Chromosomes Human X 030305 genetics & heredity Infant Newborn Infant Syndrome medicine.disease Penetrance Phenotype Products of conception Child Preschool Ubiquitin-Conjugating Enzymes Female Chromosome Deletion |
| Zdroj: | Cytogenetic and genome research. 160(5) |
| ISSN: | 1424-859X |
| Popis: | Chromosomal microdeletion syndromes present with a wide spectrum of clinical phenotypes that depend on the size and gene content of the affected region. In a healthy carrier, epigenetic mechanisms may compensate for the same microdeletion, which may segregate through several generations without any clinical symptoms until the epigenetic modifications no longer function. We report 2 novel cases of Xq24 microdeletions inherited from mothers with extremely skewed X-chromosome inactivation (sXCI). The first case is a boy presenting with X-linked mental retardation, Nascimento type, due to a 168-kb Xq24 microdeletion involving 5 genes (CXorf56, UBE2A, NKRF, SEPT6, and MIR766) inherited from a healthy mother and grandmother with sXCI. In the second family, the presence of a 239-kb Xq24 microdeletion involving 3 additional genes (SLC25A43, SLC25A5-AS1, and SLC25A5) was detected in a woman with sXCI and a history of recurrent pregnancy loss with a maternal family history without reproductive wastages or products of conception. These cases provide evidence that women with an Xq24 microdeletion and sXCI may be at risk for having a child with intellectual disability or for experiencing a pregnancy loss due to the ontogenetic pleiotropy of a chromosomal microdeletion and its incomplete penetrance modified by sXCI. |
| Databáze: | OpenAIRE |
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