DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis

Sánchez-Moreno, Irene; Canto, Patricia; Munguía, P; León, Mario Bermúdez de; Cisneros, Bulmaro; Vilchis, Felipe; Reyes, Edgardo; Méndez, Juan Pablo

doi:10.1016/j.mce.2008.10.012

Cited by 16 publications

(10 citation statements)

References 37 publications

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“…Consistent with this idea, the S143 identified as a hotspot of CTD mutations (Fig. 4b) has been proposed to contribute to DNA binding as it is predicted, using a computational protein modeling approach, to be part of a large DNA-interacting cavity and is very close to the bound DNA (Sánchez-Moreno et al 2009). Furthermore, phosphorylation of the amino acid motif 29 RRSSS 33 located in the NTD (Fig.…”

Section: Functions Of the Non-hmg-box Domains Of Srymentioning

confidence: 70%

SRY protein function in sex determination: thinking outside the box

Zhao

Koopman

2011

Chromosome Res

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Even though the mammalian sex-determining gene Sry has been intensively studied for the two decades since its discovery, the regions outside the conserved HMG box DNA-binding domain have received less attention due to a lack of sequence conservation and of obvious structural/functional motifs. Here, we summarize the available evidence for function beyond the HMG box, identify the known and postulated biochemical functions of the non-HMG-box domains in sex determination, and present possible explanations for the puzzling diversity of these non-HMG-box domains.

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Section: Functions Of the Non-hmg-box Domains Of Srymentioning

confidence: 70%

SRY protein function in sex determination: thinking outside the box

Zhao

Koopman

2011

Chromosome Res

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“…Some females diagnosed with Swyer syndrome may actually have Turner syndrome with low level mosaicism. Approximately 70-80% of patients diagnosed with Swyer syndrome do not have SRY mutations [14, 15], and Turner syndrome with low level mosaicism may be the actual cause of gonadal dysgenesis in some of these patients. In cases where conventional karyotype results do not closely match the clinical presentation, FISH analysis for low level mosaicism may be informative.…”

Section: Discussionmentioning

confidence: 99%

Mosaic Turner Syndrome Presenting with a 46,XY Karyotype

Rasouli

McDaniel

Awadalla

et al. 2019

Case Reports in Obstetrics and Gynecology

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Although Turner syndrome is most commonly associated with a 45,X genotype, other mosaic genotypes are present in approximately half of all cases. We describe a case of Turner syndrome with a 46,XY genotype by conventional 5-cell karyotype who was subsequently found to have a mosaic genotype of 18% 45,X and 82% 46,XY by 50-cell FISH analysis. Individuals with a mosaic 45,X/46,XY genotype have a variety of phenotypic presentations ranging from male to female which are not correlated with the percentage of mosaicism. Our case represents an extreme example where the genotype is predominately 46,XY and the phenotype typical of Turner syndrome.

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“…The same situations can be applied to the frameshift mutation at codons 158 and 159. It is very interesting to know that the missense mutation S143C can diminish SRY-DNA interaction [31], it mean the amino acids outside HMG domain can still influence SRY function by certain ways.…”

Section: Discussionmentioning

confidence: 99%

A Novel Missense Mutation 224G>T (R75M) in SRY Coding Region Interferes with Nuclear Import and Results in 46, XY Complete Gonadal Dysgenesis

Fan

Wang

et al. 2016

PLoS ONE

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SRY-mutation-caused sex reversal is a rare disease and mostly associated with a de novo mutation since the patients with defective SRY is infertile. There are many reports about SRY-mutation associated 46, XY ovarian disorder of sex development (DSD), but few described their molecular mechanism. Here we report a de novo mutation 224G>T (R75M) in SRY associated with a phenotypic female, 46, XY karyotype and dysgerminoma. The wild and mutated SRY were cloned into recombinant plasmid and expressed in cells in vitro, the result showed the mutated SRY is greatly accumulated in cytoplasm while the wild type SRY is mostly localized in nucleus. To make sure no other genes were involved, we performed the trio-based whole exome sequencing using the DNA samples from the proband and the parents, and no mutations were identified especially in DHH, NR0B1, NR5A1, SOX9 and MAP3K1, indicating the de novo mutation in SRY is the single defect responsible for the female sex reversal. We also used bioinformatics simulation analysis to predict impact of the mutation on SRY function, and find the R75 in wild type SRY can form a hydrogen bond with serine at 91 (S91) that make the SRY protein well fit into the minor groove of target DNA, while the M75 in the mutated SRY can’t. Finally, we reviewed SRY mutations based on the available references and analyzed the mutation distribution patterns according to density and continuity, which may be useful for further study of the SRY structure, function, and its relatedness with DSD.

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DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis

Cited by 16 publications

References 37 publications

SRY protein function in sex determination: thinking outside the box

SRY protein function in sex determination: thinking outside the box

Mosaic Turner Syndrome Presenting with a 46,XY Karyotype

A Novel Missense Mutation 224G>T (R75M) in SRY Coding Region Interferes with Nuclear Import and Results in 46, XY Complete Gonadal Dysgenesis

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