Search Results

You are looking at 1 - 2 of 2 items for :

  • Abstract: adrenarche x
  • Abstract: amenorrhoea x
  • Abstract: Gender x
  • Abstract: infertility x
  • Abstract: Klinefelter x
  • Abstract: menarche x
  • Abstract: menopause x
  • Abstract: puberty x
  • Abstract: testes x
  • Abstract: transsexual x
  • Abstract: Turner x
  • Abstract: ovary x
  • Abstract: follicles x
  • Cardiovascular x
Clear All Modify Search
Lanping Jiang Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Department of Nephrology & Key Laboratory of Nephrology, National Health Commission and Guangdong Province, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

Search for other papers by Lanping Jiang in
Google Scholar
PubMed
Close
,
Xiaoyan Peng Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Renal Division, Children’s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China

Search for other papers by Xiaoyan Peng in
Google Scholar
PubMed
Close
,
Bingbin Zhao Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Search for other papers by Bingbin Zhao in
Google Scholar
PubMed
Close
,
Lei Zhang Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Search for other papers by Lei Zhang in
Google Scholar
PubMed
Close
,
Lubin Xu Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Search for other papers by Lubin Xu in
Google Scholar
PubMed
Close
,
Xuemei Li Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Search for other papers by Xuemei Li in
Google Scholar
PubMed
Close
,
Min Nie Department of Endocrinology & Key Laboratory of Endocrinology, National Health and Family Planning Commission, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Search for other papers by Min Nie in
Google Scholar
PubMed
Close
, and
Limeng Chen Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Search for other papers by Limeng Chen in
Google Scholar
PubMed
Close

Purposes

This study was conducted to identify the frequent mutations from reported Chinese Gitelman syndrome (GS) patients, to predict the three-dimensional structure change of human Na–Cl co-transporter (hNCC), and to test the activity of these mutations and some novel mutations in vitro and in vivo.

Methods

SLC12A3 gene mutations in Chinese GS patients previously reported in the PubMed, China National Knowledge Infrastructure, and Wanfang database were summarized. Predicted configurations of wild type (WT) and mutant proteins were achieved using the I-TASSER workplace. Six missense mutations (T60M, L215F, D486N, N534K, Q617R, and R928C) were generated by site-directed mutagenesis. 22Na+ uptake experiment was carried out in the Xenopus laevisoocyte expression system. In the study, 35 GS patients and 20 healthy volunteers underwent the thiazide test.

Results

T60M, T163M, D486N, R913Q, R928C, and R959frameshift were frequent SLC12A3 gene mutations (mutated frequency >3%) in 310 Chinese GS families. The protein’s three-dimensional structure was predicted to be altered in all mutations. Compared with WT hNCC, the thiazide-sensitive 22Na+ uptake was significantly diminished for all six mutations: T60M 22 ± 9.2%, R928C 29 ± 12%, L215F 38 ± 14%, N534K 41 ± 15.5%, Q617R 63 ± 22.1%, and D486N 77 ± 20.4%. In thiazide test, the net increase in chloride fractional excretion in 20 healthy controls was significantly higher than GS patients with or without T60M or D486N mutations.

Conclusions

Frequent mutations (T60M, D486N, and R928C) and novel mutations (L215F, N534K, and Q617R) lead to protein structure alternation and protein dysfunction verified by 22Na+ uptake experiment in vitro and thiazide test on the patients.

Open access
Simon Chang Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
Department of Clinical Biochemistry, Hospital of South West Jutland, Esbjerg, Denmark
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Internal Medicine, Lillebaelt Hospital, Kolding, Denmark

Search for other papers by Simon Chang in
Google Scholar
PubMed
Close
,
Arkadiusz J Goszczak NanoSYD, The Mads Clausen Institute, University of Southern Denmark, Sønderborg, Denmark

Search for other papers by Arkadiusz J Goszczak in
Google Scholar
PubMed
Close
,
Anne Skakkebæk Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark

Search for other papers by Anne Skakkebæk in
Google Scholar
PubMed
Close
,
Jens Fedder Centre of Andrology and Fertility Clinic, Odense University Hospital, Odense, Denmark

Search for other papers by Jens Fedder in
Google Scholar
PubMed
Close
,
Anders Bojesen Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark

Search for other papers by Anders Bojesen in
Google Scholar
PubMed
Close
,
M Vakur Bor Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
Department of Clinical Biochemistry, Hospital of South West Jutland, Esbjerg, Denmark

Search for other papers by M Vakur Bor in
Google Scholar
PubMed
Close
,
Moniek P M de Maat Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
Department of Clinical Biochemistry, Hospital of South West Jutland, Esbjerg, Denmark
Department of Haematology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands

Search for other papers by Moniek P M de Maat in
Google Scholar
PubMed
Close
,
Claus H Gravholt Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark

Search for other papers by Claus H Gravholt in
Google Scholar
PubMed
Close
, and
Anna-Marie B Münster Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
Department of Clinical Biochemistry, Hospital of South West Jutland, Esbjerg, Denmark

Search for other papers by Anna-Marie B Münster in
Google Scholar
PubMed
Close

Objective

Klinefelter syndrome (KS) is associated with increased risk of thrombosis. Hypogonadism and accumulating body fat in KS have a potential impact on fibrinolysis. In this study, we assessed the fibrinolytic system and the association with testosterone levels in KS.

Design

This study is a cross-sectional comparison of men with KS and age-matched male controls.

Methods

Fibrin clot lysis was evaluated by turbidity measurements and by measuring levels of individual fibrinolytic proteins in plasma samples. Fibrin clot structure was evaluated by scanning electron microscopy. Total testosterone was measured by liquid chromatography-tandem mass spectrometry. Body fat was evaluated by dual-energy X-ray absorptiometry.

Results

In this study, 45 men with KS and 45 age- and education-matched controls were included. Men with KS had a 24% reduction in fibrin clot lysis compared with controls (46.2 ± 17.1 vs 60.6 ± 18.8 %/h, P  = 0.0003) and higher levels of fibrinogen, factor XIII (P ≤ 0.01), and plasminogen activator inhibitor type 1 (P  = 0.04). Men with KS had lower total testosterone (P  = 0.008) and higher body fat (P  = 0.001). In KS, reduced fibrin clot lysability was associated with higher fibrinogen and body fat related to decreasing total testosterone and hypogonadism among men with KS. Fibrin clot structure was not different compared to KS and controls.

Conclusions

Fibrin clot lysis in KS was markedly reduced, potentially contributing to a prothrombotic state and increasing thrombotic risk. Hypogonadism in KS was associated with increased fibrinogen and total body fat, predicting reduced fibrin clot lysis.

Open access