Prognosis of mosaic Down syndrome (cytogenetic analysis, clinical findings, childcare, education and social adaptation)

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K02497
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 09030:Childhood and nursery/pre-school education-related
• Research Institution: Tokyo Kasei University
• Principal Investigator: Takano Takako 東京家政大学, 家政学部, 教授 (50236246)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: モザイク型ダウン症候群 / モザイク率 / 染色体分析

Outline of Final Research Achievements

Cytogenetic analysis of five patients with mosaic Down syndrome (one male and four females) was carried out. G-banding and chromosome 21 fluorescence in situ hybridization (No.21 FISH) of peripheral blood cultures in four patients aged 7-23 years showed a sharp decrease in mosaicism. No.21 FISH of uncultured cells also showed a significant decrease in mosaicism. The mosaic ratio was gradually but not drastically reduced in one young child at 11 months, 2 years 9 months and 3 years 3 months of age. No. 21 FISH of oral mucosa cells (5 children) and fibroblasts cultures from tooth extraction (2 children) showed no decrease in mosaicism. The same analyses were performed in seven patients with standard trisomy 21 and one patient with translocation, all of whom maintained nearly 100% trisomy 21 cells on chromosome examination.
The clinical findings, upbringing history, education and employment status of five patients with mosaic Down syndrome were also investigated.

Free Research Field

臨床遺伝学、小児科学

Academic Significance and Societal Importance of the Research Achievements

モザイク型ダウン症患者の培養Bリンパ球と骨髄から流血中に出てきた血球細胞において、モザイク率は7歳以降で激減していた(3～8%)。3歳までは徐々にトリソミー細胞が漸減傾向にあった。造血系細胞以外の組織では、モザイク率の減少はなく、これらは学術的に新しい知見である。骨髄の中で、造血幹細胞は低酸素の微小環境（ニッチ）に存在している。骨髄中の低酸素環境はトリソミー細胞にとっては正常細胞より生存に不利に働く可能性があり、モザイク率が時間経過により減少すると推定した。
モザイク患者の生育歴、発達状況、教育・就労状況の結果は、モザイク型ダウン症患者の保育・教育、遺伝カウンセリングに資する知見と考えられる。