背景:Rubinstein-Taybi综合征(RSTS;OMIM#180849,#613684)是一种罕见的常染色体显性遗传疾病,其特征是拇指和幻觉,面部畸形,身材矮小和智力残疾程度不同。在50-60%和5-8%的病例中,RSTS与CREBBP和EP300基因突变相关,分别。大多数病例是从头杂合突变。
方法:这里我们描述一个家族性RSTS病例,与一个新的EP300突变相关。先证者是一名9岁的女性,有轻微的学习困难。她的母亲,他们也有学习困难,被发现有短而宽的拇指。进行MLPA和CREBBP和EP300的基于小组的NGS。在EP300基因的外显子31中发现了一个新的杂合移码突变(c.7222_7223del;p。(Gln2408Glufs*39))。
结论:该病例为首例遗传性EP300-RSTS。移码缺失的位置不影响HAT结构域和PHD手指,可以解释轻度表型和保存完好的智力。这些患者受到轻微影响,这个病例突出了可能的漏诊。我们建议对看起来健康的父母进行分子检测,在遗传突变的情况下,所有处于危险之中的成人一级亲属。
BACKGROUND: Rubinstein-Taybi syndrome (RSTS; OMIM #180849, #613684) is a rare autosomal dominant genetic condition characterized by broad thumbs and halluces, facial dysmorphism, short stature and variable degree of intellectual disability. RSTS is associated with mutations in CREBBP and EP300 genes in 50-60% and 5-8% of cases, respectively. The majority of cases are de novo heterozygous mutations.
METHODS: Here we describe a familial RSTS
case, associated with a novel EP300 mutation. The proband was a 9 years old female, with mild learning difficulties. Her mother, who also had learning difficulties, was found to have short and broad thumbs. MLPA and panel-based NGS of CREBBP and EP300 were performed. A novel heterozygous frameshift mutation in exon 31 of the EP300 gene (c.7222_7223del; p.(Gln2408Glufs*39)) was found in both.
CONCLUSIONS: This
case represents the first
case of inherited EP300-RSTS. The location of the frameshift deletion not affecting HAT domain and PHD finger, could explain the mild phenotype and the well-preserved intelligence. These patients are mildly affected, and this
case highlights the possible missed diagnosis. We would recommend molecular testing of apparently healthy parents, and in the
case of inherited mutations, of all adult first degree relatives at risk.