Salivary molecular diagnostics in ectodermal dysplasia
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1
Polytechnical University of Marche, Department of Clinical Specialistic and Dental Sciences, Italy
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2
University of Palermo, Department of Surgical, Oncological and Oral Sciences, Italy
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3
University of Foggia, Department of Clinical and Experimental Medicine, Italy
Aim. The WNT10A protein is critical for the development of ectodermal appendages, such as teeth, hair, and glands. Allelic variants in the WNT10A gene may be associated with a spectrum of ectodermal abnormalities including extensive tooth agenesis or hypodontia, which is described either as a clinical sign of an ectodermal dysplasia syndrome or as a non-syndromic tooth agenesis (STHAG4, OMIM 150400). In 2011, Cluzeau et al. theorized the possibility to obtain a definitive diagnosis of Ectodermal Dysplasia by WNT10A allelic variants analysis. The following is a preliminary study to establish the feasibility and the accuracy of those assumptions. The aim of this study is to assess WNT10A allelic variants by genetic analysis using salivary molecular diagnostics in patients with severe tooth agenesis and additional ectodermal symptoms.
Materials and Methods. 3 Caucasian males with oligodontia and other ectodermal symptoms diagnosed at the Regional Oral Surgery and Special Care Dentistry Unit in Ancona, Italy, were selected for the study. Two of the patients already had a definitive diagnosis of Christ-Siemens-Touraine Syndrome (OMIM 305100), while the other one was characterized by clinically uncertainty. Clinical data were compiled from patient records including photographs and panoramic radiographs. Evaluation of taurodontism of primary or permanent mandibular molars was performed using the method described by Seow and Lai. Ectodermal signs and symptoms were compiled from anamnestic data in patient records and by telephone interviews in order to obtain specific information. The patients were sampled by buccal swab and tested for mutations in the WNT10A gene. All four exons of WNT10A, exon-intron boundaries and 5′ and 3′-UTRs were PCR amplified using primers designed via the ClinVar software. Mutation screening was performed of all coding parts of the WNT10A gene by bi-directional Sanger sequencing. Chromatograms were aligned and compared to the reference sequence of the WNT10A gene (NM_025216.2).
Results. Most existing molars had taurodontism. Light, brittle or coarse hair was reported in all three individuals, hyperhidrosis of palms and soles, and nail anomalies only in those two individuals with a definitive diagnosis. The anomalies in primary dentition preceded most of the additional ectodermal symptoms. Genetic analysis revealed that patients affected by Christ-Siemens-Touraine Syndrome were homozygous or compound heterozygous for WNT10A mutations resulting in C107X, E222X and F228I, while the third one displayed only the last and most common variant.
Discussion. We conclude that tooth agenesis and/or peg-shaped crowns of primary mandibular incisors, severe oligodontia of permanent dentition as well as ectodermal symptoms of varying severity may be predictors of biallelic WNT10A mutations of importance for diagnosis, counselling and follow-up. Furthermore, we laid the groundwork for the development of a diagnostic tool based on the Clouzeau hypothesis.
References
Cluzeau C et al. Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/ anhidrotic ectodermal dysplasia cases. Hum Mutat. 2011 Jan;32(1):70-2.
Bergendal B et al. Abnormal primary and permanent dentitions with ectodermal symptoms predict WNT10A deficiency. BMC Med Genet. 2016 Nov 24;17(1):88.
Keywords:
Ectodermal Dysplasia,
WNT10A gene,
Tooth agenesis,
salivary diagnostics,
early diagnosis
Conference:
5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine., Ancona, Italy, 19 Oct - 20 Oct, 2018.
Presentation Type:
Poster Presentation
Topic:
Salivary Research
Citation:
Torelli
F,
Mascitti
M,
Panzarella
V,
Lo Muzio
L,
Santarelli
A and
Armeni
T
(2019). Salivary molecular diagnostics in ectodermal dysplasia.
Front. Physiol.
Conference Abstract:
5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine..
doi: 10.3389/conf.fphys.2019.27.00028
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Received:
24 Oct 2018;
Published Online:
09 Dec 2019.
*
Correspondence:
Dr. Marco Mascitti, Polytechnical University of Marche, Department of Clinical Specialistic and Dental Sciences, Ancona, Marche, 60121, Italy, marcomascitti86@hotmail.it