Assembling the jigsaw puzzle: CBX2 isoform 2 and its targets in disorders/differences of sex development

Molecular Genetics & Genomic Medicine
Patrick SprollAnna Biason-Lauber

Abstract

One of the defining moments of human life occurs early during embryonic development, when individuals sexually differentiate into either male or female. Perturbation of this process can lead to disorders/differences of sex development (DSD). Chromobox protein homolog 2 (CBX2) has two distinct isoforms, CBX2.1 and CBX2.2: the role of CBX2.1 in DSD has been previously established, yet to date the function of the smaller isoform CBX2.2 remains unknown. The genomic DNA of two 46,XY DSD patients was analysed using whole exome sequencing. Furthermore, protein/DNA interaction studies were performed using DNA adenine methyltransferase identification (DamID) to identify putative binding partners of CBX2. Finally, in vitro functional studies were used to elucidate the effect of wild-type and variant CBX2.2 on selected downstream targets. Here, we describe two patients with features of DSD i.e. atypical external genitalia, perineal hypospadias and no palpable gonads, each patient carrying a distinct CBX2.2 variant, p.Cys132Arg (c.394T>C) and p.Cys154fs (c.460delT). We show that both CBX2.2 variants fail to regulate the expression of genes essential for sexual development, leading to a severe 46,XY DSD defect, likely because of a defective...Continue Reading

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Citations

Jan 11, 2019·Journal of Cellular Biochemistry·Wassim Eid, Wafaa Abdel-Rehim
Apr 1, 2020·International Journal of Molecular Sciences·Nathalia Lisboa GomesRod T Mitchell
Nov 14, 2019·Scientific Reports·Patrick SprollAnna Biason-Lauber
Aug 20, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chang-Zhu PeiKwang-Hyun Baek

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Methods Mentioned

BETA
exome sequencing
Precipitation
DamID
PCR
transfection
transfecting

Software Mentioned

Pathway studio
GraphPad
GraphPad Prism
SNP
Seq
PhD
SNAP
Cytoscape
FastQC
GATK HaplotypeCaller

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