Molecular genetic study of X-linked mental retardation・αthalassemia syndrome (ATR-X)

X连锁智力低下·α地中海贫血综合征（ATR-X）的分子遗传学研究

• 批准号: 14570712
• 负责人: SAITOH Shinji
• 金额: $ 2.18万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570712/
• 关键词: ATR-X; mental retardation; DNA diagnosis; carrier diagnosis; サラセミア; ATRX

X-linked mental retardation・αthalassemia syndrome (ATR-X) is one of syndromic X-linked mental retardation, which is caused by mutations of the ATRX gene. We have investigated 27 Japanese ATR-X patients from 24 families, and identified mutations of ATRX in 24 patients from 21 families. Most mutations (14 patients from 12 families) were located in the ADD domain, while the second prevalent mutations (4 patients from 3 families) were located in helicase domain. Other minor mutations were also identified. We subsequently studied 8 mothers and identified the same mutations in 6 mothers, indicating 6/8 (75%) mothers were mutation carriers. We could examine X inactivation status using peripheral leukocytes in 4 female carries, and 3 females demonstrated skewed X inactivation pattern while one showed random pattern. The female who showed random X inactivation was associated with mild mental retardation. These findings may imply that ATRX can cause female mental retardation unless X inactivation properly inactivates the mutated X chromosome.

X连锁精神发育迟滞·α地中海贫血综合征(ATR-X)是一种由ATRX基因突变引起的X连锁精神发育迟滞综合征。我们调查了来自24个家系的27名日本ATR-X患者，并在21个家系的24名患者中发现了ATRX的突变。大多数突变(来自12个家系的14名患者)位于ADD结构域，次要突变(来自3个家系的4名患者)位于解旋酶结构域。还发现了其他一些轻微的突变。我们随后研究了8位母亲，并在6位母亲中发现了相同的突变，表明6/8(75%)的母亲是突变携带者。4例女性携带者外周血白细胞均可检测X失活状态，其中3例呈偏态X失活，1例呈随机失活。表现为随机X失活的女性与轻度精神发育迟滞有关。这些发现可能意味着ATRX会导致女性智力低下，除非X染色体失活适当地使突变的X染色体失活。

项目成果

Saitoh S, Wada T, Okajima M, Takano K, Sudo A, Niikawa N.: "Uniparental disomy and imprinting defects in Japanese patients with Angelman syndromeyferam."Brain Dev. (in press).

Saitoh S、Wada T、Okajima M、Takano K、Sudo A、Niikawa N.：“日本天使综合征患者的单亲二体性和印记缺陷。”Brain Dev。

Wada T, et al.: "Wide clinical variability in a family with a CACNA1A T666M mutation : hemiplegic migraine, coma, and progressive ataxia"Pediatr Neurol. 26. 47-50 (2002)

Wada T 等人：“具有 CACNA1A T666M 突变的家族存在广泛的临床变异：偏瘫性偏头痛、昏迷和进行性共济失调”Pediatr Neurol。

Saitoh S, Wada T, Okajima M, Takano K, Sudo A, Niikawa N: "Uniparental disomy and imprinting defects in Japanese patients with Angelman syndrome."Brain Dev. (in press).

Saitoh S、Wada T、Okajima M、Takano K、Sudo A、Niikawa N：“日本天使综合征患者的单亲二体性和印记缺陷。”Brain Dev。

Saitoh S, Hosoki K, Takano K, Sudo A: "Germline mosaicism of a novel mutation of UBE3A in Angelman syndrome"Am J Hum Genet (sup). 73. 290-290 (2003)

Saitoh S、Hosoki K、Takano K、Sudo A：“Angelman 综合征中 UBE3A 新型突变的种系嵌合”Am J Hum Genet（sup）。

Saitoh S.: "Angelman syndrome"Today's pediatric therapy, 13rd edition (in Japanese). 143 (2003)

Saitoh S.：《天使综合征》《今日儿科治疗》，第 13 版（日文）。