1q21.3 Deletion Involving GATAD2B: An Emerging Recurrent Microdeletion Syndrome
1q21.3 Deletion Involving GATAD2B: An Emerging Recurrent Microdeletion Syndrome
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DOI：
10.1002/ajmg.a.38082
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发表时间：
2017-03-01
影响因子：
2
通讯作者：
Wattanasirichaigoon, Duangrurdee
中科院分区：
文献类型：
--
作者：
Tim-Aroon, Thipwimol;Jinawath, Natini;Wattanasirichaigoon, Duangrurdee
GATAD 2B基因参与染色质修饰和转录活性。GATAD 2B的功能丧失突变最近被定义为导致可识别的智力残疾综合征（ID）。编码细丝蛋白的人TPM 3基因与肌病相关这两个基因都位于染色体1q21.3上。我们在此报告一个婴儿，有喂食困难、发育迟缓、张力减退、畸形的特徴，包括小睑裂、内眦赘皮、头发和眉毛稀疏、杯状耳和指（趾）倾。核型正常。单核苷酸多态性分析显示，染色体1q21.3的1.06Mb缺失，这被证实是从头。该缺失区包含35个基因，包括三个已知的疾病相关基因，即GATAD 2B，TPM 3和HAX 1。我们进一步确定并总结了7例额外的1q21.3微缺失患者的文献综述和临床数据库（DECIPHER，ISCA/ClinGen）。所有8例患者的基因组定位分析显示不同的断点，没有节段性重复，表明非同源末端连接是一个可能的机制，这种特殊的微缺失。这些数据表明，1q21.3微缺失是一种复发性微缺失综合征，具有可区分的表型，GATAD 2B功能丧失是特征性面容和ID的主要贡献者。此外，TPM 3的缺失保证了我们患者伴随肌肉疾病的风险。(C)2017 Wiley Periodicals，Inc.
GATAD2B gene is involved in chromatin modification and transcription activity. Loss-of-function mutations of GATAD2B have recently been defined to cause a recognizable syndrome with intellectual disability (ID). Human TPM3 gene encoding thin filament protein is associated with myopathies. Both genes are located on chromosome 1q21.3. We herein report an infant with feeding difficulty, developmental delay, hypotonia, and dysmorphic features including small palpebral fissures, telecanthus, sparse hair and eyebrow, cup-shaped ears, and clinodactyly. Karyotype was normal. Single nucleotide polymorphism array revealed a 1.06Mb deletion of chromosome 1q21.3, which was confirmed to be de novo. The deleted region encompassed 35 genes, including three known disease-associated genes, namely GATAD2B, TPM3, and HAX1. We further identify and summarize seven additional patients with 1q21.3 microdeletion from literature review and clinical databases (DECIPHER, ISCA/ClinGen). Genomic location analysis of all eight patients revealed different breakpoints and no segmental duplication, indicating that non-homologous end joining is a likely mechanism underlying this particular microdeletion. This data suggests that 1q21.3 microdeletion is a recurrent microdeletion syndrome with distinguishable phenotypes, and loss of function of GATAD2B is the major contributor of the characteristic facies and ID. Additionally, the deletion of TPM3 warrants a risk of concomitant muscle disease in our patient. (C) 2017 Wiley Periodicals, Inc.