PDF(Pubmed)
Abstract：
Schinzel-Giedion syndrome (SGS) is a severe multisystem disorder characterized by distinctive facial features, profound intellectual disability, refractory epilepsy, cortical visual impairment, hearing loss, and various congenital anomalies. SGS is attributed to gain-of-function (GoF) variants in the SETBP1 gene, with reported variants causing canonical SGS located within a 12 bp hotspot region encoding SETBP1 residues aa868-871 (degron). Here, we describe a case of typical SGS caused by a novel heterozygous missense variant, D874V, adjacent to the degron. The female patient was diagnosed in the neonatal period and presented with characteristic facial phenotype (midface retraction, prominent forehead, and low-set ears), bilateral symmetrical talipes equinovarus, overlapping toes, and severe bilateral hydronephrosis accompanied by congenital heart disease, consistent with canonical SGS. This is the first report of a typical SGS caused by a, SETBP1 non-degron missense variant. This case expands the genetic spectrum of SGS and provides new insights into genotype-phenotype correlations.
摘要：
Schinzel-Giedion综合征（SGS）是一种严重的多系统疾病，其特征是独特的面部特征，严重的智力残疾，难治性癫痫,皮质视觉障碍，听力损失,和各种先天性异常。SGS归因于SETBP1基因中的功能获得（GoF）变体，报道的变体导致位于编码SETBP1残基aa868-871（degron）的12bp热点区域内的经典SGS。这里,我们描述了一个典型的SGS由一个新的杂合错义变体引起的案例，D874V,毗邻德格隆。该女性患者在新生儿期被诊断出，并表现出特征性的面部表型（面部中缩，突出的前额,和低设定的耳朵)，双侧对称马蹄内翻足，重叠的脚趾,严重的双侧肾积水伴有先天性心脏病，与标准SGS一致。这是典型的SGS引起的第一份报告，SETBP1非degron错觉变体。此案例扩展了SGS的遗传谱，并为基因型-表型相关性提供了新的见解。
