scholarly journals Try235Phe homozygous mutation of the steroid 5-a reductase type 2 (SRD5A2) gene in a Turkish patient

2014 ◽  
Vol 34 (3) ◽  
pp. 254-256 ◽  
Author(s):  
Mesut Parlak ◽  
Erdem Durmaz ◽  
Semin Gursoy ◽  
Iffet Bircan ◽  
Sema Akcurin
Keyword(s):  
Homozygous Mutation ◽  
Turkish Patient ◽  
Srd5a2 Gene

Premature ovarian ageing following heterozygous loss of Senataxin

2020 ◽  
Author(s):  
G N Subramanian ◽  
M Lavin ◽  
H A Homer
Keyword(s):  
Dna Damage ◽  
Neurodegenerative Disorder ◽  
Dna Helicase ◽  
Dna Integrity ◽  
Ovarian Activity ◽  
Homozygous Mutation ◽  
Female Mice ◽  
Mating Trial ◽  
High Prevalence

Abstract Premature loss of ovarian activity before 40 years of age is known as primary ovarian insufficiency (POI) and occurs in ∼1% of women. A more subtle decline in ovarian activity, known as premature ovarian ageing (POA), occurs in ∼10% of women. Despite the high prevalence of POA, very little is known regarding its genetic causation. Senataxin (SETX) is an RNA/DNA helicase involved in repair of oxidative stress-induced DNA damage. Homozygous mutation of SETX leads to the neurodegenerative disorder, ataxia oculomotor apraxia type 2 (AOA2). There have been reports of POI in AOA2 females suggesting a link between SETX and ovarian ageing. Here, we studied female mice lacking either one (Setx+/−) or both (Setx−/−) copies of SETX over a 12- to 14-month period. We find that DNA damage is increased in oocytes from 8-month-old Setx+/− and Setx−/− females compared with Setx+/+ oocytes leading to a marked reduction in all classes of ovarian follicles at least 4 months earlier than typically occurs in female mice. Furthermore, during a 12-month long mating trial, Setx+/− and Setx−/− females produced significantly fewer pups than Setx+/+ females from 7 months of age onwards. These data show that SETX is critical for preventing POA in mice, likely by preserving DNA integrity in oocytes. Intriguingly, heterozygous Setx loss causes an equally severe impact on ovarian ageing as homozygous Setx loss. Because heterozygous SETX disruption is less likely to produce systemic effects, SETX compromise could underpin some cases of insidious POA.

scholarly journals Characterising SRD5A2 Gene Variants in 37 Indonesian Patients with 5-Alpha-Reductase Type 2 Deficiency

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Nanis S. Marzuki ◽  
Firman P. Idris ◽  
Hannie D. Kartapradja ◽  
Alida R. Harahap ◽  
Jose R. L. Batubara
Keyword(s):  
Autosomal Recessive ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Compound Heterozygous ◽  
Phenotypic Characteristics ◽  
Sex Development ◽  
Srd5a2 Gene ◽  
Diagnostic Approaches ◽  
Autosomal Recessive Condition

The 5-alpha-reductase type 2 deficiency (5ARD2) is an autosomal recessive condition associated with impairment in the conversion of testosterone to dihydrotestosterone. This condition leads to undervirilisation in 46,XY individuals. To date, there have been more than 100 variations identified in the gene responsible for 5ARD2 development (steroid 5-alpha-reductase 2, SRD5A2). However, few studies have examined the molecular characterisation of Indonesian 5ARD2 cases. In the current study, we analysed 37 subjects diagnosed with 46,XY DSD (disorders of sex development) with confirmed variations in the SRD5A2 gene. We examined results from testosterone/dihydrotestosterone (T/DHT) and urinary etiocholanolone/androsterone (Et/An) ratios, as well as from molecular and clinical analyses. Twelve variants in the SRD5A2 gene were identified, and 6 of which were novel, namely, c.34–38delGinsCCAGC, p.Arg50His, p.Tyr136∗, p.Gly191Arg, p.Phe194Ile, and p.Ile253Val variants. Moreover, we determined that 20 individuals contained harmful mutations, while the remaining 17 variants were benign. Those containing harmful mutations exhibited more severe phenotypes with median external genitalia masculinisation scores (EMS) of 3 (1.5–9) and were more likely to be diagnosed at a later age, reared as female, and virilised at pubertal age. In addition, the respective sensitivities for detecting severe 5ARD2 cases using T/DHT (cutoff: 10) and urinary Et/An ratios (cutoff: 0.95) were 85% and 90%, whereas mild cases were only identified with 64.7% and 47.1% sensitivity, respectively. Although we were unable to identify clear correlations between genotypic and phenotypic characteristics in this study, we clearly showed that individuals who were homozygous or compound heterozygous for any of the harmful mutations were more likely to exhibit classic 5ARD2 phenotypes, lower EMS, female assignment at birth, and virilisation during puberty. These results serve to inform the development of improved clinical and molecular 5ARD2 diagnostic approaches, specifically in Indonesian patients.

scholarly journals Steroid 5- -Reductase Type 2 (SRD5a2) Gene Polymorphisms and Risk of Prostate Cancer: A HuGE Review

2009 ◽  
Vol 171 (1) ◽  
pp. 1-13 ◽  
Author(s):  
J. Li ◽  
R. J. Coates ◽  
M. Gwinn ◽  
M. J. Khoury
Keyword(s):  
Prostate Cancer ◽  
Gene Polymorphisms ◽  
Srd5a2 Gene

scholarly journals Investigation of Methylation Alterations on SRD5A2 Gene in Patients with 5 Alpha Reductase Type 2 Enzyme Deficiency

2020 ◽  
Vol 40 (1) ◽  
pp. 68-73
Author(s):  
Emre KIRAT ◽  
Aysel KALAYCI YİĞİN ◽  
Filiz ÖZDEMİR ◽  
Mehmet SEVEN
Keyword(s):  
Enzyme Deficiency ◽  
Srd5a2 Gene

Steroid 5-alpha-reductase type 2 ( SRD5A2 ) gene V89L polymorphism and hypospadias risk: A meta-analysis

2017 ◽  
Vol 13 (6) ◽  
pp. 630.e1-630.e9 ◽  
Author(s):  
K. Zhang ◽  
Y. Li ◽  
Y. Mao ◽  
M. Ma
Keyword(s):  
Meta Analysis ◽  
Srd5a2 Gene

scholarly journals Comorbidity between progressive familial intrahepatic cholestasis and atopic dermatitis in a 19-month-old child

2019 ◽  
Vol 12 (10) ◽  
pp. e230152
Author(s):  
Ilenia Panasiti ◽  
Silvana Briuglia ◽  
Stefano Costa ◽  
Lucia Caminiti
Keyword(s):  
Atopic Dermatitis ◽  
Intrahepatic Cholestasis ◽  
Skin Lesions ◽  
Homozygous Mutation ◽  
Gamma Glutamyl Transpeptidase ◽  
Poor Growth ◽  
Adequate Treatment ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
Chronic Skin

Atopic dermatitis (AD) is the most common chronic skin disease in children, with an increasing prevalence in the past three decades. Adequate treatment is prescribed for individual patient based on symptoms and disease severity. However, further underlying diagnosis should be researched when therapeutic strategies for symptoms fail and skin lesions and pruritus persist. We reported herein the case of a 19-month-old infant with a history of AD unresponsive to treatment due to the type 2 progressive familial intrahepatic cholestasis (PFIC). A new homozygous mutation of the ABCB11 gene was found. The severe pruritus, the early onset jaundice, poor growth and raised transaminase levels with normal gamma glutamyl transpeptidase have led to the suspicion of PFIC. The presence of severe AD and intrahepatic chronic cholestasis, both pruritus associated, could delay a proper diagnosis. To our knowledge, for the first time, a case of comorbidity between type 2 PFIC and AD-like disease had been described.

scholarly journals Accuracy of Urinary Etiocholanolone/Androsterone Ratio as Alternative to Serum Testosterone/Dihydrotestosterone Ratio for Diagnosis of 5 Alpha-reductase Type 2 Deficiency Patients and Carriers in Indonesia

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Nanis Sacharina Marzuki ◽  
Firman Pratama Idris ◽  
Hannie Kartapradja ◽  
Shirley Renata ◽  
Alida Harahap ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Disorders Of Sex Development ◽  
Cost Benefit ◽  
Serum Testosterone ◽  
Diagnostic Value ◽  
Roc Curve Analysis ◽  
Sex Development ◽  
Srd5a2 Gene ◽  
Alternative Test

Background: The 5 Alpha-reductase type 2 deficiency (5ARD2) is an inherited condition, which clinically presents as variable degrees of under virilization in affected 46,XY individuals. In the diagnostic pathway of 5ARD2, the testosterone/dihydrotestosterone (T/DHT) ratio is broadly employed before molecular analysis of the SRD5A2 gene. However, due to cost-benefit considerations, the DHT test in our country is routinely lacking in clinical settings; therefore, we considered applying the urinary etiocholanolone/androsterone (Et/An) ratio as an alternative test. Objectives: We aimed to determine the diagnostic value of the urinary Et/An ratio versus the T/DHT ratio in diagnosing 5ARD2 patients and carriers. Methods: Sixty-six suspected 5ARD2 46,XY disorders of sex development (DSD) individuals and 95 family members were recruited in the study. Their physical manifestations, T/DHT and urinary Et/An ratios, and SRD5A2 genes were analyzed. Using molecular analysis of the SRD5A2 gene as the gold standard, we compared the accuracy of both ratios in diagnosing 5ARD2 patients and carriers with receiver operating characteristic (ROC) curve analysis. Results: Thirty-seven patients were confirmed molecularly to have 5ARD2, and the rest (n = 29) were assessed as normal controls, while in the carrier group, 53 were molecularly confirmed as carriers and 42 as controls. The AUCs (areas under the curve) of the T/DHT and urinary Et/An ratios were 57.7% (95% CI 43.0 - 72.4%, P > 0.05) and 79.7% (95% CI 69.0 - 90.4%, P < 0.001), respectively, in diagnosing 5ARD2 patients and 54.1% (95% CI 42.4 - 65.8%, P > 0.05) and 75.1% (95% CI 65.1 - 85.1%, P < 0.001), respectively, in diagnosing carriers. The cutoff value of the urinary Et/An ratio was set at ≥ 0.95 for detecting 5ARD2 patients and ≥ 0.99 for detecting carriers. Conclusions: The testosterone/DHT ratio was inaccurate in diagnosing 5ARD2 patients. When molecular analysis for the SRD5A2 gene is lacking, the urinary Et/An ratio may be a useful test to diagnose 5ARD2 patients and carriers.

scholarly journals MassARRAY Multigene Screening Combined with LDL-C and sdLDL-C Detection for more Favorable Outcomes in type 2 Diabetes Mellitus Therapy

2020 ◽  
Author(s):  
Yong Tian ◽  
Junhong Wang ◽  
Yanxiao Liu ◽  
Xiangguang Luo ◽  
Ziying Yao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Gene Polymorphisms ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Disease Course ◽  
Healthy Individuals ◽  
Clinical Value ◽  
Before And After

Abstract Background: To determine the clinical value of multigene polymorphisms, LDL-C and sdLDL-C on T2DM therapy.Methods: In total, 352 T2DM patients before and after treatment and 48 healthy individuals were enrolled in this study. LDL-C and sdLDL-C were detected in 352 T2DM patients and 48 healthy individuals by Quantimetrix Lipoprint System. The 11 gene polymorphisms—HTR3B (rs2276307, A>G), APOE (rs7412, c.526C>T), APOE (rs429358, c.388T>C), CYP2C9*3 (rs1057910, c.1075A>C), KIF6 (rs20455, c.2155T>C), HMGCR (rs17238540, T>G), HMGCR (rs17244841, A>T), ABCB1 (rs2032582, c.2677G > T/A), HTR7 (rs1935349, C>T), SLCO1B1 (rs4149056, c.521T>C), and CETP (rs708272, G>A)—were screened in these 352 T2DM patients by the Agena Bioscience MassARRAY system before therapy.Results: Genetic polymorphisms associated with T2DM and statin effects in pretreatment patients were detected, then results showed that all 11 genes had heterozygous mutation, and 7 genes had homozygous mutation in 352 T2DM patients, more specifically reflected that these gene polymorphisms were common in Chinese T2DM patients. LDL-C and sdLDL-C were detected before and after treatment, sdLDL mainly existed in T2DM patients, and T2DM patients had higher mean levels of sdLDL-C than healthy people. After pharmacotherapy, the coincidence rates of decreases in LDL-C and sdLDL-C levels were 88.35% (311/352) and 84.09% (296/352), consistent with patients in remission.Conclusions: Gene polymorphisms related to pharmacotherapy were common in Chinese T2DM patients. And the expression of LDL-C and sdLDL-C was consistent with the T2DM disease course. Combined multigene screening before therapy and LDL-C and sdLDL-C detection before and after therapy could better assist T2DM treatment.

scholarly journals Apparent mineralocorticoid excess syndrome in a Brazilian boy caused by the homozygous missense mutation p.R186C in the HSD11B2 gene

2008 ◽  
Vol 52 (8) ◽  
pp. 1277-1281 ◽  
Author(s):  
Fernanda Borchers Coeli ◽  
Lúcio Fábio Caldas Ferraz ◽  
Sofia H. V. de Lemos-Marini ◽  
Sumara Zuanazi Pinto Rigatto ◽  
Vera Maria Santoro Belangero ◽  
...  
Keyword(s):  
Mineralocorticoid Receptor ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Homozygous Mutation ◽  
Molecular Studies ◽  
Apparent Mineralocorticoid Excess ◽  
Gene Maps ◽  
Apparent Mineralocorticoid Excess Syndrome

The apparent mineralocorticoid excess syndrome (AME) is a rare autosomal recessive disorder due to the deficiency of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2). The 11beta-HSD2 enzyme, encoded by HSD11B2 gene, metabolizes active cortisol in cortisone. Mutations on HSD11B2 gene affect the enzyme activity by leading to an excess of cortisol, which causes its inappropriate access to mineralocorticoid receptor. Therefore, cortisol will bind mineralocorticoid receptor. The human HSD11B2 gene maps to chromosome 16q22 and consists of five exons encoding a protein of 405 amino acids. We present here clinical and molecular studies on a Brazilian boy who was born pre-term after an oligodramnious pregnancy. He was diagnosed as having AME at the age of 26 months. His parents are second cousins. Molecular characterization of the HSD11B2 gene revealed the homozygous mutation p.R186C. The patient described here is the second case of HDS11B2 gene mutation reported in Brazilian patients with AME.

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