2017
DOI: 10.1159/000478718
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Functional Analysis of Mutations at Codon 127 of the <b><i>SRY</i></b> Gene Associated with 46,XY Complete Gonadal Dysgenesis

Abstract: Complete gonadal dysgenesis (CGD) is characterized by an incomplete differentiation of the genital organs in a patient with a 46,XY karyotype. It is induced by mutations in the sex-determining region Y (SRY) gene which plays a key role in testis-determining pathways. The aim of this study was to investigate the possible pathogenic nature of a novel SRY mutation (p.Y127H) identified in a 46,XY female patient. To determine the effect of this mutation on SRY function, we studied its impact on DNA interaction by e… Show more

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Cited by 7 publications
(12 citation statements)
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“…Such attenuated DNA bending must represent a transmitted effect of the mutations as the WT side chain, and presumably also the variant side chains, is not in direct contact with the bent DNA site. These DNA bend angles each fall, however, within the range of WT species variation (60), so altered DNA bending is unlikely to be responsible for either the variant proteins' loss of transcriptional activity in cell culture or associated DSD phenotypes (44,45).…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Such attenuated DNA bending must represent a transmitted effect of the mutations as the WT side chain, and presumably also the variant side chains, is not in direct contact with the bent DNA site. These DNA bend angles each fall, however, within the range of WT species variation (60), so altered DNA bending is unlikely to be responsible for either the variant proteins' loss of transcriptional activity in cell culture or associated DSD phenotypes (44,45).…”
Section: Discussionmentioning
confidence: 99%
“…(B) Rigid-body substitution of mutant side chains at box position 72 (sticks) in an otherwise transparent CPK model. Models of the three clinical mutants ( 34 , 44 , 45 ): Y127C in red, Y127F in orange and Y127H in green.…”
Section: Introductionmentioning
confidence: 99%
“…SRY pathogenic variants affect DNA binding, bending or cellular localization of the TDF. Impaired nucleus transportation of the TDF and failure of a transcriptional complex assembly result in a disrupted sex differentiation cascade [ 10 ]. Patients with SRY -associated complete gonadal dysgenesis commonly have a female phenotype.…”
Section: Discussionmentioning
confidence: 99%
“…Whatever the pattern nsSNPs take in the interruption of SRY activity, these three risky nsSNPs were found to be associated with several sex reversal issues [62,65,66]. However, I90M and Y127F undergo their deleterious tasks by a straightforward effect on structure, function, and stability without being intervened in the modulation of SRY binding with its DNA receptor.…”
Section: Discussionmentioning
confidence: 99%