Maritime Medical Genetics Services, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada.
Am J Med Genet A. 2012 Jan;158A(1):182-7. doi: 10.1002/ajmg.a.34355. Epub 2011 Nov 21.
Timothy syndrome (TS) is an autosomal dominant condition with the constellation of features including prolonged QT interval, hand and foot abnormalities, and mental retardation or autism. Splawski et al. [2004] previously described two phenotypes associated with TS distinguished by two unique and different mutations within the CACNA1C gene. We report on a newborn who presented with prolonged QT interval and associated polymorphic ventricular tachycardia, dysmorphic facial features, syndactyly of the hands and feet, and joint contractures, suggestive of TS. He developed a stroke, subsequent intractable seizures, and was found to have cortical blindness and later profound developmental delay. Initial targeted mutation analysis did not identify either of the previously described TS associated mutations; however, full gene sequencing detected a novel CACNA1C gene mutation (p.Ala1473Gly). The clinical and genetic findings in our case expand both the clinical and molecular knowledge of TS.
Timothy 综合征（TS）是一种常染色体显性遗传病，其特征包括 QT 间期延长、手足异常以及智力迟钝或自闭症。Splawski 等人[2004]先前描述了两种与 TS 相关的表型，其特征是 CACNA1C 基因内存在两个独特且不同的突变。我们报告了一名新生儿，其表现为 QT 间期延长以及相关的多形性室性心动过速、面部畸形、手足并指畸形、关节挛缩，提示 TS。他发生了中风，随后出现难治性癫痫发作，被发现患有皮质盲，后来出现严重的发育迟缓。初步的靶向突变分析未发现先前描述的任何一种 TS 相关突变；然而，全基因测序检测到一种新的 CACNA1C 基因突变（p.Ala1473Gly）。我们病例的临床和遗传发现扩展了 TS 的临床和分子知识。
