A newly identified missense mutation of the EDA1 gene in a Hungarian patient with Christ–Siemens–Touraine syndrome

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.

Oligodontia in the Clinical Spectrum of Syndromes: A Systematic Review

“…The networks included 18 predicted interactions (Figure 2). Christ-Siemens-Touraine syndrome (#305100) Permanent 18 12,14, 15, 18, 22, 24, 25, 28, 31, 32, 34, 35, 38, 41, 42, 44, 45, 48 Abs, Raes and Vercruysse (1994) Wolff-Parkinson-White syndrome (#194200) Permanent 15 14, 15, 17, 18, 12, 22, 25, 27, 28, 35, 37, 38, 45, 47, 48 Aditya, Lele and Aditya (2011) Fahr's syndrome (#213600) Permanent 16 11,14, 15, 17, 21, 35, 36, 37, 38, 42, 43, 44, 45, 46, 47, 48 Agarwal et al (2014) Polycistic ovarian syndrome (#184700) Permanent 26 12,13,14,15,16,17,18,22,23,25,27,28,31,32,33,34,35,37,38,41,42,44,45,46,47,48 Aminabadi, Ebrahii and Oskouei (2010) Ellis-van Creveld syndrome (#225500) Primary / Permanent 6 / 9 52, 53, 63, 71, 73, 83 / 12, 31, 32, 33, 35, 41, 42, 43, 45 Ann Drum et al (1985) Rieger syndrome (#602482) Permanent 19 11, 12, 13, 14, 16, 18, 21, 22, 23, 26, 28, 31, 32, 33, 36, 41, 42, 45, 46 Ardila and Álvarez-Martínez (2022) Axenfeld-Rieger syndrome (#601499, #180500, #602482) Permanent 22 16, 15, 14, 13, 12, 21 ,22, 25, 26, 31, 32, 33, 34, 35, 36, 37, 41, 42, 43, 44, 45, 46 Arora et al (2016) Witkop syndrome (#189500) Permanent 26 11,12,14,15,16,…”

“…51, 52, 54, 61, 62, 64, 74, 84 / 11, 12, 13, 14, 15, 21, 22, 23, 24, 25, 33, 34, 43, 44 4. 54, 62, 63, 64, 71, 81, 84 / 11, 12, 14, 15, 21, 22, 23, 24, 25, 31, 32, 33, 35, 41, 42, 43, 44 Barber et al (2012) Carvajal syndrome (#605676) Permanent 13 15, 17, 18, 24, 25, 27, 28, 35, 37, 38, 45, 47, 48 Bekiesinska-Figatowska et al (2010) Hypomyelination, hypogonadotropic hypogonadism, hypodontia syndrome (4H) (#612440) Permanent 8 12, 15, 22, 24, 34, 35, 44, 45 Bergendal (2001) Hypohidrotic ectodermal dysplasia (#305100) Permanent 16 13, 14, 15, 24, 25, 31, 32, 33, 34, 35, 38, 41, 42, 43, 44, 45 Bergendal et al (2015) X-linked hypohidrotic ectodermal dysplasia (#300291) Permanent 28 11,12,14,15,17,18,21,22,24,25,27,28,31,32,33,34,35,36,37,38,41,42,43,44,45,46,47,48 Bildik et al ( 2012) Hypohidrotic ectodermal dysplasia (#305100) Permanent 30 12, 13, 14, 15, 16, 17, 18, 22, 23, 24, 25, 26, 27, 28, 31, 32, 33, 34, 35, 36, 37, 38, 41, 42, 43, 44, 45, 46, 47, 48 Blankenstein et al (2001) Carpenter syndrome (#201000) Permanent 22 12, 14, 15, 17, 18, 22, 24, 25, 27, 28, 31, 32, 34, 35, 37, 38, 41, 42, 44, 45, 47, 48 Cagetti et al (2019) Progeroid syndrome (#612289) Permanent 26 11, 12, 14, 15, 16, 17, 18, 21, 22, 23, 24, 25, 26, 27, 28, 33, 34, 36, 37, 38, 43, 44, 45, 46, 47, 48 Callanan, Anand and Sheehy (2006) Sotos syndrome (#117550) Permanent 15…”

Oligodontia in the Clinical Spectrum of Syndromes: A Systematic Review

“…However, many of the included studies in this systematic review did not perform molecular analysis. Only 23 studies [41,43,52,53,56,63,[66][67][68]70,73,74,76,78,79,[87][88][89][90]92,94,98,105] performed genetic analysis and reported the genetic variants associated with the syndromes. These genes can be grouped into two major groups: one with crucial roles at multiple stages of tooth development, also involving skin and sweat glands (AXIN2, CDH1, DSP, EDA, EDARADD, EVC2, FGFR2, LEF1, MSX1, PITX2, and WNT10A), which are involved in the signal pathway essential for ectodermal structure development [121,122]; the other with genes that intermediate cellular function and development (NPHP1, PCNT, PTCH1, IKBKG, SRCAP, and TBCE).…”