Abstract
Christ–Siemens–Touraine syndrome (CST; OMIM 305100) belongs to the group of ectodermal dysplasias and is characterized by the development of sparse hair, abnormal or missing teeth and sweating deficiency. CST is the consequence of mutations located in the ectodysplasin A (EDA1) gene. We have identified a 35-year-old Hungarian man with characteristic dysmorphic facial features, sparse hair, reduced sweating and missing teeth. Direct sequencing of the coding regions revealed a novel missense mutation in the eighth exon (c.971T/A, p.Val324Glu). The affected patient carries the mutation in a hemizygous form. Previous studies reported the association of missense mutations with non-syndromic tooth agenesis. However, the reported hemizygous patient exhibits hypodontia as well as hypotrichosis and reduced sweating. His daughter, an obligate heterozygous carrier of the identified missense mutation, exhibits only mild teeth abnormalities. As the novel missense mutation is located within the tumor necrosis factor (TNF) domain of the ectodysplasin protein, we hypothesize that this genetic variant affects the ectodysplasin/NFκB signaling pathway.
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References
Bal E, Baala L, Cluzeau C et al (2007) Autosomal dominant anhidrotic ectodermal dysplasias at the EDARADD locus. Hum Mutat 28:703–709
Chassaing N, Bourthoumieu S, Cossee M et al (2006) Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic ectodermal dysplasia. Hum Mutat 27:255–259
Clauss F, Manière MC, Obry F et al (2008) Dento-craniofacial phenotypes and underlying molecular mechanisms in hypohidrotic ectodermal dysplasia (HED): a review. J Dent Res 87:1089–1099
Cluzeau C, Hadj-Rabia S, Jambou M et al (2011) Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases. Hum Mutat 32:70–77
Courtney JM, Blackburn J, Sharpe PT (2005) The ectodysplasin and NFκB signalling pathways in odontogenesis. Arch Oral Biol 50:159–163
Knaudt B, Volz T, Krug M et al (2012) Skin symptoms in four ectodermal dysplasia syndromes including two case reports of Rapp–Hodgkin-syndrome. Eur J Dermatol 22:605–613
Li S, Li J, Cheng J et al (2008) Non-syndromic tooth agenesis in two Chinese families associated with novel missense mutations in the TNF domain of EDA (ectodysplasin A). PLoS ONE 3:e2396
Monreal AW, Zonana J, Ferguson B (1998) Identification of a new splice form of the EDA1 gene permits detection of nearly all X-linked hypohidrotic ectodermal dysplasia mutations. Am J Hum Genet 63:380–389
Tao R, Jin B, Guo SZ et al (2006) A novel missense mutation of the EDA gene in a Mongolian family with congenital hypodontia. J Hum Genet 51:498–502
Wedgeworth EK, Nagy N, White JM et al (2011) Intra-familial variability of ectodermal defects associated with WNT10A mutations. Acta Derm Venereol 91:346–347
Zhang H, Quan C, Sun LD et al (2009) A novel frameshift mutation of the EDA1 gene in a Chinese Han family with X-linked hypohidrotic ectodermal dysplasia. Clin Exp Dermatol 34:74–76
Zhang J, Han D, Song S et al (2011) Correlation between the phenotypes and genotypes of X-linked hypohidrotic ectodermal dysplasia and non-syndromic hypodontia caused by ectodysplasin-A mutations. Eur J Med Genet 4:377–382
Acknowledgments
The following grants are acknowledged: TÁMOP-4.2.2/B-10/1/KONV-2010-0012 grant, TÁMOP-4.2.2.A-11/1/KONV-2012-0035 grant, OTKA PD104782 2012-2015 grant. Nikoletta Nagy is supported by Janos Bolyai Scholarship 2011–2014.
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The authors declare that they have no conflict of interest.
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Á. Kinyó and P. Vályi contributed equally to this work.
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Kinyó, Á., Vályi, P., Farkas, K. et al. A newly identified missense mutation of the EDA1 gene in a Hungarian patient with Christ–Siemens–Touraine syndrome. Arch Dermatol Res 306, 97–100 (2014). https://doi.org/10.1007/s00403-013-1408-8
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DOI: https://doi.org/10.1007/s00403-013-1408-8