التفاصيل البيبلوغرافية
| العنوان: |
Case Report: De novo DDX3X mutation caused intellectual disability in a female with skewed X-chromosome inactivation on the mutant allele |
| المؤلفون: |
Sun, Yixi, Qian, Yangwen, Sun, Hai-Xi, Chen, Min, Luo, Yuqin, Xu, Xiaojing, Yan, Kai, Wang, Liya, Hu, Junjie, Dong, Minyue |
| المصدر: |
Frontiers in Genetics ; volume 13 ; ISSN 1664-8021 |
| بيانات النشر: |
Frontiers Media SA |
| سنة النشر: |
2022 |
| المجموعة: |
Frontiers (Publisher - via CrossRef) |
| مصطلحات موضوعية: |
Genetics (clinical), Genetics, Molecular Medicine |
| الوصف: |
Skewed XCI plays an important role in the phenotypic heterogeneities of many X-linked disorders, even involving in diseases caused by XCI-escaping genes. DDX3X -related intellectual disability is more common in females and less common in males, who usually inherit from unaffected heterozygous mothers. As an X inactivation (XCI) escaping gene, the role of skewed XCI in the phenotype of DDX3X mutant female is unknown. Here we reported a DDX3X : c.694_711dup18 de novo heterozygous mutation in a female with intellectual disability on the maternal X chromosome on the basis of SNPs detected by PCR-sanger sequencing. AR assay revealed that the maternal mutant X chromosome was extremely inactivated in the proband. Using RNA sequencing and whole-exome sequencing, we quantified allelic read counts and allele-specific expression, and confirmed that the mutant X chromosome was inactive. Further, we verified that the mutant DDX3X allele had a lower expression level by RNA sequencing and RT-PCR, and the normal and mutated DDX3X expression accounted for respectively 70% and 30% of total. In conclusion, we found a symptomatic female with extreme skewing XCI in the DDX3X mutant allele. It was discovered that XCI in the mutant allele was insufficient to reverse the phenotype of DDX3X -related neurodevelopmental disorder. It contributed to a better understanding of the role of skewed XCI in phenotypic differences, which can aid in the genetic counseling and prenatal diagnosis of disorders in females with DDX3X defects. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| DOI: |
10.3389/fgene.2022.999442 |
| DOI: |
10.3389/fgene.2022.999442/full |
| الإتاحة: |
https://doi.org/10.3389/fgene.2022.999442Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.69590BAA |
| قاعدة البيانات: |
BASE |
