Comprehensive genotyping of Turkish women with hirsutism

Abstract

Introduction Hirsutism is a medical sign rather than a disease affects 5-8% of women of reproductive age. Hirsutism is associated with hyperandrogenemia in most patients excluding those with idiopathic hirsutism (IH). The most common cause of hirsutism is polycystic ovary syndrome (PCOS) followed by IH and idiopathic hyperandrogenemia (IHA); however, the clinical presentation of non-classical congenital adrenal hyperplasia (NCAH) in females is often indistinguishable from other hyperandrogenic disorders with common clinical signs such as hirsutism. Objective The primary aim of the study is to examine the physical properties of the three genes and to make a detailed comparison of the mutations with the clinical data to contribute the etiology of hirsutism. Subjects and Methods 122 women admitted to the Endocrinology Clinic at Erciyes University Hospital with hirsutism were enrolled in the study between 2013-2014. All the participants were clinically evaluated. Protein-encoding exons, exon-intron boundaries of CYP21A2 (including proximal promoter), CYP11B1 and HSD3B2 genes were analyzed via state-of-the-art genetic studies. Results DNA sequencing analyses revealed two homozygous and three compound heterozygous 21-hydroxylase deficient (21OHD) NCAH patients. Additionally, three novel CYP21A2 mutations (A89V, M187I and G491S) and two novel CYP11B1 mutations (V188I and G87A) were determined. The frequencies of heterozygous mutations in CYP21A2 (including promoter), CYP11B1 and HSD3B2 genes were determined as 26.5% (15% coding region, 11.5% promoter), 11.5% and 0%, respectively. Conclusion 21OHD-NCAH prevalence was determined to be ~4%. Unexpectedly, high heterozygous mutation rates were observed in CYP11B1 gene and CYP21A2 promoter region. CYP11B1 and HSD3B2 deficiencies were not prevalent in Turkish women with hirsutism despite the existence of higher heterozygous mutation rate in CYP11B1.

17-Hydroxyprogesterone Response to Standard Dose Synacthen Stimulation Test in CYP21A2 Heterozygous Carriers and Non-carriers in Symptomatic and Asymptomatic Groups: Meta-analyses

“…These studies were carried out in Europe, the United States of America, and Russia. Three studies were carried out in Greece ( 15 , 30 , 31 ), three in the United States of America ( 18 , 32 , 33 ), two in Italy ( 34 , 35 ), two in Brazil ( 36 , 37 ), two in France ( 38 , 39 ), one in Turkey ( 21 ), one in Russia ( 40 ) and one in Israel ( 41 ). CYP21A2 mutation analysis and basal and/or stimulated 17-OHP measurements were available in all study subjects.…”

“…Determination of carrier status is also compulsory for genetic counselling of the parents affected by CAH/NCAH and in families that includes a parent with confirmed heterozygous mutation, since genetic counselling plays an important role in the control of genetic diseases. The heterozygous individuals may be diagnosed with NCAH due to false-positivity of the SDSST, especially in V281L heterozygous mutation ( 21 ). Therefore, there is a need for up-to-date studies on the specificity and sensitivity of the SDSST to distinguish CYP21A2 carriers and 21OHD-NCAH.…”

“…The prevalence of asymptomatic carriers for the disease in the general population was estimated to range from 1:50 to as high as 1:16 ( 24 ) and even higher among Ashkenazi Jews, according to a single report ( 8 ). The frequency of mutation carriers of CYP21A2 was almost 1 in 4 in PP and hirsute groups ( 21 , 25 ).…”

“…A consensus is not available about whether heterozygous individuals with CYP21A2 mutations have a higher risk of developing clinical hyperandrogenism. In some selected populations, being heterozygous for CYP21A2 seems to be related to irregular menses, hirsutism, PCOS, premature adrenarche (PA), acne, and central precocious puberty ( 12 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ). In contrast, other investigators concluded that heterozygosity for CYP21 mutations did not increase the risk of clinical androgen excess above that expected in the general population ( 22 , 23 ).…”

Determination of Self-Esteem, Sexual Self-Efficacy, Anxiety and Depression Levels of Women With Hirsutism Determinarea Stimei De Sine, a Autoeficacității Sexuale, a Nivelului De Anxietate Și Depresie a Femeilor Cu Hirsutism

“…In studies examining the genetic structure of Anatolia, it was found that hirsutism is a common problem, and in some accompanying clinical findings it was reported to have negative effects on life and marriage. (Salman KE, 2017;Polat S, 2019;Demir B, 2011) This study was conducted to investigate the self-esteem, sexual self-efficacy, anxiety and depression levels of women with hirsutism.…”