Case Report: De novo DDX3X mutation caused intellectual disability in a female with skewed X-chromosome inactivation on the mutant allele
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 mother...
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Veröffentlicht in: | Frontiers in genetics 2022-10, Vol.13 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 1664-8021 1664-8021 |
DOI: | 10.3389/fgene.2022.999442 |