CBX2 gene analysis in patients with 46 XY and 46 XX gonadal disorders of sex development

CBX2 gene disruption, described in one case of 46,XY ovarian disorder of sex development (DSD), is not a common cause of other gonadal DSD forms.

Ameli Norling, M.D., Angelica Lindén Hirschberg, M.D., Ph.D., Erik Iwarsson, M.D., Ph.D., Anna Wedell, M.D., Ph.D., Michela Barbaro, Ph.D.

Volume 99, Issue 3, Pages 819-826.e3, 1 March 2013


To investigate a cohort of patients with gonadal disorders of sex development (DSD) for causative CBX2 gene mutations and or gene copy number changes.

Genetic association study.

University laboratory and tertiary university-based referral center.

Forty-seven patients with different forms of 46,XY or 46,XX gonadal DSD.

CBX2 gene sequencing and development of a synthetic probe set for multiplex ligation probe amplification (MLPA) to detect CBX2 copy number changes. RTPCR to evaluate CBX2 expression in two different cell line types.

Main Outcome Measures:
Gene sequence alteration and or partial or complete gene copy number variations. Detection of CBX2 mRNA isoforms.

Ten sequence alterations were detected, 9 reported single nucleotide polymorphisms (SNPs) and a previously unreported variant. This was a silent c.1356G>A transition which may represent a normal variant. A rare SNP (c.1411C>G, p.471Pro>Ala), was found in heterozygous form in one patient. No deletions or duplications were detected by MLPA. Expression of both CBX2 mRNA isoforms was documented in gonadal fibroblasts and EBV-transformed lymphocytes.

No pathogenic CBX2 mutation was detected. Both CBX2 isoforms are expressed in gonadal fibroblasts and EBV-transformed lymphocytes. This study does not support CBX2 gene disruption as a common cause of gonadal DSD.

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