A novel SRY gene mutation c.266 A>T (p.E89V) in a 46,XY complete gonadal dysgenesis patient

Abstract

The SRY gene is considered as the key player in the male sexual differentiation and developmental pathway. SRY gene mutations account for ~15% of 46,XY disorders of sexual development patients, and majority of them resides within the HMG domain of the protein. In this study, we report a novel missense mutation within the HMG domain of SRY gene, and an A-to-T transition causes E89V amino acid substitution in a 15-year-old female patient with 46,XY karyotype and complete gonadal dysgenesis.Moreover, three-dimensional analysis of protein-DNA complex showed that the replacement of highly hydrophilic glutamic acid residue with a hydrophobic residue like valine would have an impact on the structure of protein. In conclusion, we identified a novel SRY mutation in a 46,XY female patient with complete gonadal dysgenesis, and based on the protein modelling, we propose that the identified mutation could impair normal function of the SRY protein. K E Y W O R D Sgonadal dysgenesis, HMG domain, SRY

SRY and NR5A1 gene mutation in Algerian children and adolescents with DSD and testicular dysgenesis

“…Direct sequencing of the whole SRY coding region revealed no mutation in all patients studied. Mutations in the SRY gene have been described in patients with DSD 5 , 37 – 43 . Mutations involving the SRY gene are almost exclusively associated with complete rather than partial gonadal dysgenesis and this may explain the lack of SRY mutations in this cohort.…”

“Waking up” the sleeping metaphor of normality in connection to intersex or DSD: a scoping review of medical literature

“…The study of Lepais and colleagues criticized the new DSD classification system for not taking into account histological anomalies (Lepais et al, 2016). Five studies used a term derived from intersex: intersexuality (Carsote et al, 2016;Mazen, 2017), intersex variation (Rich et al, 2016), intersex condition (Raveendran et al, 2019) or intersex disorder (Chowdhury et al, 2018;Raveenthiran, 2017;Teklu et al, 2016), not in the sense of an identity to be proud of, but rather as a more outdated medical concept for physical sex ambiguities. One paper (Roen et al, 2018) expressed its critique on the term "disorder" by placing it between hyphens.…”

“…normal vagina, normal penis, normal ovaries, normal testes, normal labia, normal ovarian tubes, normal fallopian tubes, abnormality of scrotum). Only in some occasions did the authors explain in more detail why these organs were considered (ab)normal, namely in terms of appearance (Adrião et al, 2020;Barham et al, 2016;Chen et al, 2018;Chowdhury et al, 2018;Fadil Iturralde et al, 2020;Hernández et al, 2016;Nasir et al, 2019;Ochi et al, 2019;Özdemir et al, 2019;Patil et al, 2019;Roth et al, 2018;Schteingart et al, 2019;Weaver et al, 2019), size (Adrião et al, 2020;Marei et al, 2016;Matsumoto et al, 2017;Mondal et al, 2016;Rich et al, 2016;Schteingart et al, 2019), length (AbouZeid & Mohammad, 2020;Finlayson et al, 2019;Goncalves et al, 2019;Morandi et al, 2018;Raveenthiran, 2017;van Leeuwen et al, 2019), location (Finlayson et al, 2019), and function (Heo et al, 2018;Lepais et al, 2016;Poyrazoglu et al, 2017;Raveendran et al, 2019;Raveenthiran, 2017). Some examples include: normal looking genitalia, normal appearing uterus, normal penis size, abnormal enlargement of clitoris, vagina with normal length, normally descended testes, abnormal location of the urethral meatus, and normal testicular function.…”

“…Many papers (Caputo et al, 2019;Heo et al, 2018;Hunter et al, 2016;Kearsey & Hutson, 2017;Larios García & Bautista Delgado, 2016;Patil et al, 2019;Poyrazoglu et al, 2017;Raveenthiran, 2017;Rich et al, 2016;Saikia et al, 2019;Schteingart et al, 2019;Şimşek et al, 2016;Singh et al, 2016;Touzon et al, 2019;Wagner-Mahler et al, 2019;Yan et al, 2019) also referred to (ab) normal hormonal levels or (ab)normal hormone production (e.g. testosterone, estrogen, luteinizing hormone (LH), follicle stimulating hormone (FSH), Anti-Müllerian hormone (AMH)), at times with the indication of a reference range (Adrião et al, 2020;Morandi et al, 2018;Raveendran et al, 2019;Şimşek et al, 2016;Sperling & Meyer, 2017;Teasdale & Morton, 2017;Wu et al, 2017;Xu et al, 2018). A few articles (Heo et al, 2018;Khare et al, 2017;Larios García & Bautista Delgado, 2016;Mirshahvalad et al, 2018;Özdemir et al, 2019;Pranckėnienė et al, 2019) also referred to secondary sex characteristics such as breasts (e.g.…”