Loeys-Dietz综合征(LDS)是一种罕见的多系统疾病,以血管和骨骼异常为特征,具有相当大的家族内和家族间变异性。
我们报道了一个8岁男性的病例,该病例具有两种不同的遗传性疾病的临床特征,即LDS,在最初的几个月表现为进行性主动脉根扩张,动脉弯曲,双歧悬垂,腹股沟疝和眼皮肤白化病(OCA)表现为白发和皮肤不晒黑,眼球震颤,减少虹膜色素与虹膜半透明,和减少视网膜色素)。我们确定了以前的报道,TYR的纯合突变,c.1A>G(p。Met1Val)和杂合,TGFBR1的错义突变,c.1460G>A(p。Arg487Gln)。家族史显示,他的母亲因源自颊动脉的复发性出血而接受了多次手术修复。分子研究证实了母系遗传的低等级TGFBR1突变体细胞镶嵌(外周血白细胞中18%,口腔细胞占18%,毛根细胞占10%)。母亲的心脏检查显示出独特的心血管特征:主动脉弓轻度弯曲,近端腹主动脉扩张,多个左心室深心肌隐窝,和发育不良的二尖瓣.已经在携带TGFBR2突变的孩子的三个父亲中描述了TGFBR2种系镶嵌性,但是,据我们所知,到目前为止,尚未报道母体遗传的TGFBR1突变镶嵌现象。
此病例报告表明,患有躯体镶嵌症的个体可能有轻度和不寻常形式的LDS的风险,但种系镶嵌症可以导致后代疾病的全面描述。
Loeys-Dietz syndrome (LDS) is a rare multisystemic disorder characterized by vascular and skeletal abnormalities, with considerable intra- and interfamilial variability.
We report the
case of an 8-year-old male with clinical features of two distinct genetic disorders, namely LDS, manifesting in the first months by progressive aortic root dilatation, arterial tortuosity, bifid uvula, and inguinal hernias and oculocutaneous albinism (OCA) manifesting by white hair and skin that does not tan, nystagmus, reduced iris pigment with iris translucency, and reduced retinal pigment). We identified previously reported, homozygous mutations of TYR, c.1A > G (p.Met1Val) and heterozygous, missense mutation of
TGFBR1, c.1460G > A (p.Arg487Gln). Family history revealed that his mother underwent multiple surgical repairs for recurrent hemorrhage originating from the buccal artery. Molecular studies confirmed a maternally inherited low grade
TGFBR1 mutation somatic mosaicism (18% in peripheral blood leukocytes, 18% in buccal cells and 10% in hair root cells). Maternal cardiac investigations revealed peculiar cardiovascular features: mild tortuosity at the aortic arch, dilatation of the proximal abdominal aorta, multiple deep left ventricular myocardial crypts, and dysplastic mitral valve. TGFBR2 germline mosaicism has been described in three fathers of children carrying TGFBR2 mutations but, to the best of our knowledge, no
case of maternally inherited
TGFBR1 mutation mosaicism has been reported so far.
This case report suggests that individuals with somatic mosaicism might be at risk for mild and unusual forms of LDS but germline mosaicism can lead to full blown picture of the disease in offspring.