A novel pathogenic mutation in TSPEAR associated with sensorineural hearing loss: a case report and review of the literature

BACKGROUND: Thrombospondin type laminin G domain and epilepsy associated repeats is a protein involved in the expression of genes associated with the Notch signaling pathway that have major roles in ectodermal differentiation and neural tissue development; variants in thrombospondin type laminin G domain and epilepsy associated repeats have been shown to be associated with a variety of clinical presentations including dysplasia in the skin, nail, sweat glands, hair, or teeth and hearing abnormalities. CASE PRESENTATION: Herein we report a patient presenting with bilateral profound sensorineural hearing loss. The patient was a 6-year-old Iranian girl of Fars ethnicity, born to a consanguineous marriage, who had flat audiogram in pure tone audiometry obtained from both ears and absence of any response in auditory brain response. We examined the patient for any form of ectodermal dysplasia or malformation in teeth, skin, hair, and nail and they were in normal figuration. In this study, a novel homozygous pathogenic variant in thrombospondin type laminin G domain and epilepsy associated repeats was identified (NM_144991.3: c.668C > T, p. Ser223Leu) using whole exome sequencing. CONCLUSION: Thrombospondin type laminin G domain and epilepsy associated repeats mutation presenting solely with hearing issues and lack of any ectodermal dysplasia was rare based on the review of previously reported cases. Given the high importance of these genetic disorders and the burden associated with them, the family members of these patients should pursue molecular genetic tests to identify the carriers and eliminate the risk of future occurrence of these phenotypes.