2019 Fiscal Year Final Research Report
Elucidation of prevalence, clinical features and pathogenic mechanism of PDZD7 mutations which was identified as a novel gene causing nonsyndromic hearing loss
| Project/Area Number |
18K19626
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
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| Research Institution | 独立行政法人国立病院機構(東京医療センター臨床研究センター) |
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Principal Investigator |
Matsunaga Tatsuo 独立行政法人国立病院機構(東京医療センター臨床研究センター), 聴覚・平衡覚研究部, 部長 (90245580)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Keywords | 非症候群性難聴 / PDZD7 / 次世代シークエンサー / PDZドメイン / USH2複合体 / アッシャー症候群 |
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| Outline of Final Research Achievements |
We genetically analyzed 336 individuals in 334 families, registered as hearing-loss patients who have no other symptoms, with the onsets at 15 years old or under, and with unknown etiology after our routine analysis. Seven patients in 6 families had biallelic variants in PDZD7, a deafness gene. Including 4 patients in 2 families, which were previously detected, the patients exhibited that the onset was at 4 years of age or earlier. Most of the patients showed moderate-level of hearing loss. Variant curation revealed that the 3 variants among the 5 detected ones were pathogenic or likely pathogenic. We constructed expression vectors for green fluorescence protein- and/or 3xflag-tagged PDZD7 and WHRN, which is a protein associated with PDZD7. The vectors are used for in-vitro functional assays to elucidate deficiencies in formation of the protein complexes in the hearing-loss patients.
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| Free Research Field |
耳鼻咽喉科学
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| Academic Significance and Societal Importance of the Research Achievements |
現在、次世代シークエンサーの利用によって、一人の患者に多くの遺伝子変異が見つかっているが、エビデンスを基に変異の病的意義を明らかにすることは正しい病態の理解に重要である。今回我々はPDZD7という難聴遺伝子の変異の頻度・病的意義、さらには、典型的な症状、今後の進行の可能性を明らかにした。遺伝情報は、今のところ一生変えることのできない器質であり、患者本人だけでなく家族にも影響する。精度の高い情報により、難聴の原因を特定し、その病態を明らかにすることは、今後の病態の変化を予測し、それに対して医学的に備える一助となる。また、将来の治療法の開発に役立つとともに、難聴者と社会の相互理解にも役立つ。
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