S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Ph.D. / Sc.D._의학과)
Molecular Etiology of Hereditary Single Side Deafness: Its Association with Pigmentary Disorders and Waardenburg Syndrome
일측성 난청의 분자유전학적 원인: 색소 이상 질환과 와덴버그증후군과의 관련성
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- unilateral sensorineural hearing loss; single side deafness; heritability; pigmentary disorder; Waardenburg syndrome
- 학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2017. 2. 오승하.
- Introduction: Unilateral sensorineural hearing loss (USNHL)/single side deafness (SSD) is a frequently encountered disability in children. The etiology of a substantial portion of USNHL/SSD still remains unknown, and genetic causes have not been clearly elucidated. In this study, the authors evaluated the heritability of USNHL/SSD.
Methods: The authors sequentially recruited 50 unrelated children with SSD. For an etiologic diagnosis, we performed a rigorous review on the phenotypes of family members of all children and conducted, if necessary, molecular genetic tests including targeted exome sequencing of 129 deafness genes and whole exome sequencing.
Results: Among the 50 SSD children cohort, the authors identify four (8%) unrelated SSD probands from four families (SH136, SB173, SB177, and SB199) with another hearing impaired family members. Notably, all four probands in our cohort with a familial history of SSD also have pigmentary abnormalities such as brown freckles or premature gray hair within 1st degree relatives, which may indicate that genes whose products are involved with pigmentary disorder could be candidates for heritable SSD. Indeed, SH136 and SB199 turned out to segregate a mutation in MITF and PAX3, respectively, leading to a molecular diagnosis of Waardenburg syndrome (WS).
Conclusion: We report, for the first time in the literature, a significant heritability of pediatric SSD. There is a strong association between the heritability of USNHL/SSD and the pigmentary abnormality, shedding a new light on the understanding of the molecular basis of heritable USNHL/SSD. In case of children with congenital SSD, it would be mandatory to rigorously screen pigmentary abnormalities. WS should also be included in the differential diagnosis of children with USNHL/SSD, especially in a familial form.