背景:TNRC6B缺乏症,也称为语音和行为异常的全球发育迟缓(MIM619243),是一种罕见的常染色体显性遗传病,主要表现为面部畸形,发育迟缓/智力残疾(DD/ID),言语和语言延迟,精细和电机延迟,注意缺陷多动障碍(ADHD),和可变的行为异常。它是由TNRC6B基因(NM_001162501.2,MIM610740)中的杂合变体引起的,其编码含有三核苷酸重复的衔接子6B蛋白。
方法:在本研究中,招募了两名患有TNRC6B缺乏症的中国患者,从这些父母及其家庭成员的外周血白细胞中提取基因组DNA,用于全外显子组测序和Sanger测序。
结果:这里,我们报告了两名无关的中国患者,这些患者被诊断为由新的从头可能致病性或致病性TNRC6B变异c.335C>T引起的TNRC6B缺乏综合征(p。Pro112Leu)和c.1632delC(p。Leu546fs*63),扩大了TNRC6B缺乏症的遗传谱。患者的临床特征为DD/ID,说话延迟,多动症,行为异常,身材矮小,体重低,咖啡厅-au-lait斑点,代谢异常,和面部畸形,包括粗糙的面部特征,稀疏的头发,额前带,超端粒,弱视,斜视,和下倾斜的睑裂,这扩展了与TNRC6B缺乏症相关的表型谱。
结论:本研究扩展了TNRC6B缺陷综合征的基因型和表型谱。我们的发现表明,应监测TNRC6B缺乏症患者的生长和代谢问题,并应制定治疗策略来解决这些问题。我们的报告还表明了TNRC6B缺乏症的临床多样性。
BACKGROUND: TNRC6B deficiency syndrome, also known as global developmental delay with speech and behavioral abnormalities (MIM 619243), is a rare autosomal dominant genetic disease mainly characterized by facial dysmorphism, developmental delay/intellectual disability (DD/ID), speech and language delay, fine and motor delay, attention deficit and hyperactivity disorder (ADHD), and variable behavioral abnormalities. It is caused by heterozygous variant in the TNRC6B gene (NM_001162501.2, MIM 610740), which encodes the trinucleotide repeat-containing adaptor 6B protein.
METHODS: In this study, two Chinese patients with TNRC6B deficiency syndrome were recruited, and genomic DNA extraction from peripheral blood leukocytes of these parents and their family members was extracted for whole-exome sequencing and Sanger sequencing.
RESULTS: Here, we report two unrelated Chinese patients diagnosed with TNRC6B deficiency syndrome caused by novel de novo likely pathogenic or pathogenic TNRC6B variants c.335C>T (p.Pro112Leu) and c.1632delC (p.Leu546fs*63), which expands the genetic spectrum of TNRC6B deficiency syndrome. The clinical features of the patients were DD/ID, delayed speech, ADHD, behavioral abnormalities, short stature, low body weight, café-au-lait spots, metabolic abnormalities, and facial dysmorphism including coarse facial features, sparse hair, frontal bossing, hypertelorism, amblyopia, strabismus, and downslanted palpebral fissures, which expands the phenotype spectrum associated with TNRC6B deficiency syndrome.
CONCLUSIONS: This study expands the genotypic and phenotypic spectrum of TNRC6B deficiency syndrome. Our findings indicate that patients with TNRC6B deficiency syndrome should be monitored for growth and metabolic problems and therapeutic strategies should be developed to address these problems. Our report also suggests the clinical diversity of TNRC6B deficiency syndrome.