Sweating ability and genotype in individuals with X-linked hypohidrotic ectodermal dysplasia

被引:43
作者
Schneider, Holm [1 ]
Hammersen, Johanna [1 ]
Preisler-Adams, Sabine [2 ]
Huttner, Kenneth [3 ]
Rascher, Wolfgang [1 ]
Bohring, Axel [2 ]
机构
[1] Univ Erlangen Nurnberg, German Competence Ctr Children Ectodermal Dysplas, Dept Pediat, D-91054 Erlangen, Germany
[2] Univ Munster, Inst Human Genet, D-4400 Munster, Germany
[3] Edimer Pharmaceut Inc, Cambridge, MA USA
关键词
EDA GENE; ECTODYSPLASIN-A; MISSENSE MUTATION; SKIN-CONDUCTANCE; TOOTH AGENESIS; HYPODONTIA; FAMILIES; INFANTS; PROTEIN; DOMAIN;
D O I
10.1136/jmg.2010.084012
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background X-linked hypohidrotic ectodermal dysplasia (XLHED), the most common type of ectodermal dysplasia, is caused by EDA gene mutations. Reduced sweating contributes substantially to XLHED associated morbidity and mortality. To characterise the genotype-phenotype relationship, sweat gland function was assessed non-invasively in XLHED patients and healthy controls. Subjects and methods In 36 genotyped XLHED patients and 29 control subjects aged 0-57 years, pilocarpine-induced sweat volume, palmar sweat pore density, and palmar skin conductance before and after stimulation were determined. Results Among 31 XLHED males, 14 had neither detectable sweat pores nor inducible sweating, 10 showed a few sweat pores but absent sweating, and 7 produced reduced sweat volumes (1-11 mu l) as compared with controls (38-93 mu l). Two of the low sweating XLHED subjects had normal sweat pore counts. In all 5 heterozygous females, some sweat was detected, but generally less than in female controls. Basal and stimulated skin conductance readings were reduced in 23 of 24 non-sweating, but only in 3 of 12 low-sweating XLHED subjects. There was no correlation between sweat production and number of missing teeth. Conclusions In contrast to prior reports on non-genotyped hypohidrotic ectodermal dysplasia populations, this study confirmed a consistent, quantifiable defect of sweat gland function in male XLHED subjects as a disease biomarker. Among 26 different EDA genotypes, specific mutations were shown to be consistently associated with anhidrosis, implying that systematic mapping of EDA mutations together with the analysis of objective clinical data may help to distinguish functionally crucial mutations from those allowing residual activity of the gene product.
引用
收藏
页码:426 / 432
页数:7
相关论文
共 22 条
[1]   The anhidrotic ectodermal dysplasia gene (EDA) undergoes alternative splicing and encodes ectodysplasin-A with deletion mutations in collagenous repeats [J].
Bayés, M ;
Hartung, AJ ;
Ezer, S ;
Pispa, J ;
Thesleff, I ;
Srivastava, AK ;
Kere, J .
HUMAN MOLECULAR GENETICS, 1998, 7 (11) :1661-1669
[2]   Prevalence and prevention of severe complications of hypohidrotic ectoderrnal dysplasia in infancy [J].
Blueschke, Gert ;
Nuesken, Kai-Dietrich ;
Schneider, Holm .
EARLY HUMAN DEVELOPMENT, 2010, 86 (07) :397-399
[3]   WNT10A Mutations Are a Frequent Cause of a Broad Spectrum of Ectodermal Dysplasias with Sex-Biased Manifestation Pattern in Heterozygotes [J].
Bohring, Axel ;
Stamm, Thomas ;
Spaich, Christiane ;
Haase, Claudia ;
Spree, Kerstin ;
Hehr, Ute ;
Hoffmann, Mandy ;
Ledig, Susanne ;
Sel, Saadettin ;
Wieacker, Peter ;
Roepke, Albrecht .
AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 85 (01) :97-105
[4]   Mutations within a furin consensus sequence block proteolytic release of ectodysplasin-A and cause X-linked hypohidrotic ectodermal dysplasia [J].
Chen, YW ;
Molloy, SS ;
Thomas, L ;
Gambee, J ;
Bächinger, HP ;
Ferguson, B ;
Zonana, J ;
Thomas, G ;
Morris, NP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (13) :7218-7223
[5]   Ectodysplasin is a collagenous trimeric type II membrane protein with a tumor necrosis factor-like domain and co-localizes with cytoskeletal structures at lateral and apical surfaces of cells [J].
Ezer, S ;
Bayés, M ;
Elomaa, O ;
Schlessinger, D ;
Kere, J .
HUMAN MOLECULAR GENETICS, 1999, 8 (11) :2079-2086
[6]   Mutations in the EDA gene are responsible for X-linked hypohidrotic ectodermal dysplasia and hypodontia in Chinese kindreds [J].
Fan, Huali ;
Ye, Xiaoqian ;
Shi, Lisong ;
Yin, Wei ;
Hua, Bo ;
Song, Guangtai ;
Shi, Bin ;
Bian, Zhuan .
EUROPEAN JOURNAL OF ORAL SCIENCES, 2008, 116 (05) :412-417
[7]   Scarcity of mutations detected in families with X linked hypohidrotic ectodermal dysplasia: diagnostic implications [J].
Ferguson, BM ;
Thomas, NST ;
Munoz, F ;
Morgan, D ;
Clarke, A ;
Zonana, J .
JOURNAL OF MEDICAL GENETICS, 1998, 35 (02) :112-115
[8]   Novel EDA mutation resulting in X-linked non-syndromic hypodontia and the pattern of EDA-associated isolated tooth agenesis [J].
Han, Dong ;
Gong, Yu ;
Wu, Hua ;
Zhang, Xiaoxia ;
Yan, Ming ;
Wang, Xiaozhu ;
Qu, Hong ;
Feng, Hailan ;
Song, Shujuan .
EUROPEAN JOURNAL OF MEDICAL GENETICS, 2008, 51 (06) :536-546
[9]   Skin conductance as a measure of pain and stress in hospitalised infants [J].
Harrison, Denise ;
Boyce, Suzanne ;
Loughnan, Peter ;
Dargaville, Peter ;
Storm, Hanne ;
Johnston, Linda .
EARLY HUMAN DEVELOPMENT, 2006, 82 (09) :603-608
[10]   Skin conductance changes during the first year of life in full-term infants [J].
Hernes, KG ;
Morkrid, L ;
Fremming, A ;
Odegården, S ;
Martinsen, OG ;
Storm, H .
PEDIATRIC RESEARCH, 2002, 52 (06) :837-843