Exome and RNA-Seq analyses of an incomplete penetrance variant in USP9X in female-specific syndromic intellectual disability.

Autor: Li D; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., March ME; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Wang T; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Merengwa V; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Sertori Finoti L; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Schrier Vergano SA; Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia, USA.; Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia, USA., Hakonarson H; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Bhoj EJ; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2022 Jun; Vol. 188 (6), pp. 1808-1814. Date of Electronic Publication: 2022 Mar 07.
DOI: 10.1002/ajmg.a.62715
Abstrakt: Pathogenic variants in USP9X, on X chromosome, have been implicated in syndromic intellectual disability (ID) in both males and females with distinct craniofacial features. We report a truncating variant, c.885_889delAAAAG, p.(Lys296Serfs*4), in the USP9X gene with incomplete penetrance in two nontwin female siblings with phenotypic resemblance to female-specific syndromic ID (MIM 300969, also known as MRX99F). To investigate the possible genetic etiology of the reduced penetrance, X-inactivation, RNA-Seq, and full quad exome analyses were attempted, but failed to identify a promising candidate modifier. While the penetrance of pathogenic variants in USP9X in female appears to be high (95%) and the variants frequently occur de novo, incomplete penetrance should be considered.
(© 2022 Wiley Periodicals LLC.)
Databáze: MEDLINE
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