17α-Hydroylase/17,20-lyase deficiency related to P.Y27*(c.81C&gt;A) mutation in CYP17A1 gene

Keskin, Mahmut; Uğurlu, Aylin Kılınç; Savaş‐Erdeve, Şenay; Sağsak, Elif; Akyüz, Sare Gülfem; Çeti̇nkaya, Semra; Aycan, Zehra

doi:10.1515/jpem-2014-0444

Cited by 16 publications

(18 citation statements)

References 10 publications

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“…CYP17A1 gene mutations associated with 17-OHD previously reported from Turkey are: large deletions exons 1-6 (eight patients from two different families) (11,12), stop codon mutation p.Y27*(c.81C>A) in exon 1 (two patients from different families) (13,14), R239Q(G>A) exon not-known (one patient) (15), and a point mutation c.1307G>A (one patient) (16). …”

Section: Discussionmentioning

confidence: 99%

Delayed Diagnosis of a 17-Hydroxylase/17,20-Lyase Deficient Patient Presenting as a 46,XY Female: A Low Normal Potassium Level Can Be an Alerting Diagnostic Sign

Çamtosun

Şıklar²,

Ceylaner³

et al. 2017

Jcrpe

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17-hydroxylase/17,20-lyase deficiency (17-OHD), a rare autosomal recessive defect in adrenal and gonadal steroidogenesis, causes absence of secondary sexual characteristics and frequently associated with hypertension and hypokalemia. Here, we report a 46,XY case who had normal potassium levels and no hypertension. Our patient was a 2.5-year-old female admitted with female external genitalia and inguinal swelling. Pathology of biopsy revealed that this gonad was a testis. Karyotype was 46,XY. She had no hypertension and no hypokalemia. Serum luteinizing hormone and follicle-stimulating hormone levels were high; testosterone, dehydroepiandrosterone sulfate, and androstenedione were low. Human chorionic gonadotrophin stimulation resulted in partial testosterone response. She was initially diagnosed as partial gonadal dysgenesis or testosterone synthesis defect. In her follow-up after noticing low normal potassium levels at age 9 years, progesterone level was measured and detected to be high. Adrenocorticotropic hormone-stimulated steroid measurements were consistent with 17-OHD. Genetic analyses revealed p. R96Q (c.287G>A) homozygous mutation on exon 1 of CYP17A1 gene. In conclusion, evaluation of 46,XY disorder of sex development patients must include serum potassium levels, and near low levels of potassium levels should also suggest 17-OHD despite absence of hypertension or remarkable hypokalemia. Testosterone synthesis defects must be excluded before establishing the diagnosis of partial gonadal dysgenesis.

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Section: Discussionmentioning

confidence: 99%

Delayed Diagnosis of a 17-Hydroxylase/17,20-Lyase Deficient Patient Presenting as a 46,XY Female: A Low Normal Potassium Level Can Be an Alerting Diagnostic Sign

Çamtosun

Şıklar²,

Ceylaner³

et al. 2017

Jcrpe

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“…Additionally, protein structure analysis has been done to examine the impact of specific mutants on a form of CAH known as salt-water wasting disease, which if left undiagnosed leads to low sodium levels and death (Haider et al, 2013). CYP17A1 is heavily involved in steroidogenesis, with deletion mutations leading to hormone production inhibition and sex development abnormalities (Keskin et al, 2015;Turkkahraman et al, 2015;Zhang et al, 2015;Papi et al, 2018;Xia et al, 2021). Recent genome studies of 17OHD patients revealed 46,XY karyotype in physically presenting females which cooccur with multiple mutations in the CYP17A1 gene (Zhang et al, 2015;Xia et al, 2021).…”

Section: Investigation Of Outlier Genes Associated With Genital Morphologymentioning

confidence: 99%

Evolution of genes involved in the unusual genitals of the bear macaque,Macaca arctoides

Stevison

Szpiech

Bailey

et al. 2020

Preprint

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13Genital divergence contributes to reproductive barriers between species. Emergence of a 14 novel accessory structure, the baculum, has independently evolved and been lost throughout 15 mammalian evolution, purportedly driven by sexual selection. In primates, the longest recorded 16 baculum belongs to Macaca arctoides, the bear macaque. This species has been proposed to be of 17 homoploid hybrid origin via ancient hybridization between representatives from the fascicularis 18 and sinica species groups. To investigate the evolutionary origins of the bear macaque and its 19 unique morphology, we used whole genome sequences to quantify gene flow and phylogenetic 20 relationships in 10 individuals from 5 species, including the bear macaque (n=3), and two species 21 each from the sinica (n=3) and fascicularis (n=4) species groups. The results of these analyses were 22 concordant, and identified 608 genes in the bear macaque that supported both clustering between 23 M. arctoides and the sinica group (topo2) and had shared derived alleles between species from the 24 two groups. Similarly, 361 genes supported both clustering between M. arctoides and the 25 fascicularis group (topo3) and had shared derived alleles between both groups. Further, sliding 26 window analysis of phylogenetic relationships revealed 53% of the genomic regions supported 27 placement of M. arctoides in the sinica species group (topo2), 16% supported placement in the 28 fascicularis species group (topo3), and 11% supported M. arctoides in a grouping distinct from the 29 sinica and fascicularis groups (topo1). Genomic regions with topo1 were intersected with 30 previously identified QTL for mouse baculum morphology, and 47 genes were found, including five 31 of sixteen major candidate loci that govern mouse baculum variation (KIF14, KIAA0586, RHOJ, 32 TGM2, and DACT1). Although baculum morphology in the bear macaque is diverged from its parent 33 taxa, it most closely resembles that of the fascicularis group. Outliers of shared ancestry from the 34 fascicularis species group located within these same QTL regions overlap with the gene BMP4, 35 which is an important component of the hedgehog signaling pathway that controls gonadogenesis. 36Two additional outlier genes (one shared with each species group) outside of the baculum QTL are 37 known to interact with BMP4, suggesting this pathway may be involved in baculum morphology in 38 primates. These results highlight how the mosaic ancestry of the bear macaque could explain its 39 unique baculum evolution and collectively contribute to reproductive isolation. 40 Introductory Paragraph 41In mammals, the baculum has extreme morphological variability, a dynamic evolutionary 42 history characterized by repeated gain and loss, and is often used in species identification. The bear 43 macaque has divergent genital morphology, including the longest baculum among all primates, and 44 is proposed to have evolved via ancient hybrid speciation. Here, population genetic and 45 phylogenomic approaches were used to e...

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“…Additionally, protein structure analysis has been done to examine the impact of specific mutants on a form of CAH known as the salt‐water wasting disease, which if left undiagnosed leads to low sodium levels and death (Haider et al, 2013 ). CYP17A1 is heavily involved in steroidogenesis, with deletion mutations leading to hormone production inhibition and sex development abnormalities (Keskin et al, 2015 ; Papi et al, 2018 ; Turkkahraman et al, 2015 ; Xia et al, 2021 ; Zhang et al, 2015 ). Recent genome studies of 17OHD patients revealed 46,XY karyotypes in physically presenting females which co‐occur with multiple mutations in the CYP17A1 gene (Xia et al, 2021 ; Zhang et al, 2015 ).…”

Section: Resultsmentioning

confidence: 99%

Evolution of genes involved in the unusual genitals of the bear macaque, Macaca arctoides

Stevison

Bailey

Szpiech

et al. 2022

Ecology and Evolution

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Genital divergence is thought to contribute to reproductive barriers by establishing a “lock‐and‐key" mechanism for reproductive compatibility. One such example, Macaca arctoides , the bear macaque, has compensatory changes in both male and female genital morphology as compared to close relatives. M . arctoides also has a complex evolutionary history, having extensive introgression between the fascicularis and sinica macaque species groups. Here, phylogenetic relationships were analyzed via whole‐genome sequences from five species, including M . arctoides , and two species each from the putative parental species groups. This analysis revealed ~3x more genomic regions supported placement in the sinica species group as compared to the fascicularis species group. Additionally, introgression analysis of the M . arctoides genome revealed it is a mosaic of recent polymorphisms shared with both species groups. To examine the evolution of their unique genital morphology further, the prevalence of candidate genes involved in genital morphology was compared against genome‐wide outliers in various population genetic metrics of diversity, divergence, introgression, and selection, while accounting for background variation in recombination rate. This analysis identified 67 outlier genes, including several genes that influence baculum morphology in mice, which were of interest since the bear macaque has the longest primate baculum. The mean of four of the seven population genetic metrics was statistically different in the candidate genes as compared to the rest of the genome, suggesting that genes involved in genital morphology have increased divergence and decreased diversity beyond expectations. These results highlight specific genes that may have played a role in shaping the unique genital morphology in the bear macaque.

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17α-Hydroylase/17,20-lyase deficiency related to P.Y27*(c.81C>A) mutation in CYP17A1 gene

Cited by 16 publications

References 10 publications

Delayed Diagnosis of a 17-Hydroxylase/17,20-Lyase Deficient Patient Presenting as a 46,XY Female: A Low Normal Potassium Level Can Be an Alerting Diagnostic Sign

Delayed Diagnosis of a 17-Hydroxylase/17,20-Lyase Deficient Patient Presenting as a 46,XY Female: A Low Normal Potassium Level Can Be an Alerting Diagnostic Sign

Evolution of genes involved in the unusual genitals of the bear macaque,Macaca arctoides

Evolution of genes involved in the unusual genitals of the bear macaque, Macaca arctoides

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