Expanding the spectrum of syndromic PPP2R3C‐related XY gonadal dysgenesis to XX gonadal dysgenesis. Issue 2 (17th November 2021)

• Record Type: Journal Article
• Authors: Altunoglu, Umut; Börklü, Esra; Shukla, Anju; Escande‐Beillard, Nathalie; Ledig, Susanne; Azaklı, Hülya; Nayak, Shalini S.; Eraslan, Serpil; Girisha, Katta Mohan; Kennerknecht, Ingo; Kayserili, Hülya
• Is Part Of: Clinical genetics. Volume 101:Issue 2(2022)
• Page Start: 221
• Page End: 232
• Publication Date: 2021-11-17
• Subjects: disorders of sexual development -- facial dysmorphism -- PPP2R3C -- XX gonadal dysgenesis -- XY gonadal dysgenesis; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.14086
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract: Homozygous variants in PPP2R3C have been reported to cause a syndromic 46, XY complete gonadal dysgenesis phenotype with extragonadal manifestations (GDRM, MIM# 618419) in patients from four unrelated families, whereas heterozygous variants have been linked to reduced fertility with teratozoospermia (SPGF36, MIM# 618420) in male carriers. We present eight patients from four unrelated families of Turkish and Indian descent with three different germline homozygous PPP2R3C variants including a novel in‐frame duplication (c.639_647dupTTTCTACTC, p.Ser216_Tyr218dup). All patients exhibit recognizable facial dysmorphisms allowing gestalt diagnosis. In two 46, XX patients with hypergonadotropic hypogonadism and nonvisualized gonads, primary amenorrhea along with absence of secondary sexual characteristics and/or unique facial gestalt led to the diagnosis. 46, XY affected individuals displayed a spectrum of external genital phenotypes from ambiguous genitalia to complete female. We expand the spectrum of syndromic PPP2R3C ‐related XY gonadal dysgenesis to both XY and XX gonadal dysgenesis. Our findings supported neither ocular nor muscular involvement as major criteria of the syndrome. We also did not encounter infertility problems in the carriers. Since both XX and XY individuals were affected, we hypothesize that PPP2R3C is essential in the early signaling cascades controlling sex determination in humans. Abstract :