A Novel Pathogenic TSPEAR Variant in a Family with Clinical Variability: Definition of Dental Anomalies and Review of the Literature
Molecular Syndromology, cilt.16, sa.4, ss.291-310, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 16 Sayı: 4
- Basım Tarihi: 2025
- Doi Numarası: 10.1159/000544806
- Dergi Adı: Molecular Syndromology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE
- Sayfa Sayıları: ss.291-310
- Anahtar Kelimeler: Alopecia, Dysmorphic features, Ectodermal dysplasia, Tooth agenesis, TSPEAR
- Hacettepe Üniversitesi Adresli: Evet
Özet
Introduction: Ectodermal dysplasias (EDs) represent a heterogeneous group of genetic disorders marked by impaired development of multiple tissue derivatives originating from the human ectoderm, including teeth, hair, nails, and sweat glands. Advances in next-generation sequencing technology have facilitated the identification of novel genes, such as TSPEAR, contributing to the emergence of the ectodermal dysplasia-14 of the hair/tooth type (ECTD14) phenotype, primarily characterized by hypotrichosis, hypodontia, and dysmorphic features. Methods: Five individuals from the same family were included in the study, three of whom were heterozygous and two homozygous for a novel frameshift TSPEAR variant. All displayed ED and/or tooth loss. Exome sequencing was performed in the index case, and Sanger sequence analysis was carried out to detect the carrier status in parents and relatives. Results: We identified a novel biallelic frameshift TSPEAR variant [NM_144991.2, c.1594_1595insA, p.(Phe532TyrfsTer26)] in two siblings who displayed oligodontia, sparse hair, and facial dysmorphism. The remaining heterozygous carriers manifested early tooth loss with non-syndromic isolated oligodontia. Conclusion: This study has identified individuals carrying biallelic and heterozygous TSPEAR variants, where heterozygous carriers often exhibit non-syndromic tooth agenesis. Moreover, the presence of inter- and intrafamilial variability emerges as a notable feature of the disease. This understanding underscores the complexity of the disease and the importance of considering genetic variability when diagnosing and managing affected individuals.