Malerba Natascia, Towner Shelley, Keating Katherine, Squeo Gabriella Maria, Wilson William, Merla Giuseppe
Division of Medical Genetics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Division of Medical Genetics, University of Virginia, Charlottesville, VA, United States.
Front Genet. 2018 Dec 12;9:626. doi: 10.3389/fgene.2018.00626. eCollection 2018.
Homozygous and compound heterozygous pathogenic variants in have been recently associated with a spectrum of clinical presentations varying from a severe multisystem form of the disorder including intellectual disability, early infantile developmental and epileptic encephalopathy, retinal abnormalities and cardiac arrhythmias (IDDCA) to a milder form with language delay, attention-deficit/hyperactivity disorder, cognitive impairment, with or without cardiac arrhythmia (LADCI). Approximately twenty patients have been described so far; here we report a novel case of a 2.5-year-old female who is a compound heterozygote for a frameshift and a missense variant in the gene. Her clinical presentation is consistent with a moderate phenotype, corroborating the direct correlation between the type and pathogenic mechanism of the genetic variant and the severity of related phenotype.
最近发现，[基因名称]中的纯合和复合杂合致病变异与一系列临床表现相关，从严重的多系统疾病形式，包括智力残疾、早期婴儿发育和癫痫性脑病、视网膜异常和心律失常（IDDCA）到较轻的形式，伴有语言发育迟缓、注意力缺陷/多动障碍、认知障碍，有或无心律失常（LADCI）。迄今为止，大约已描述了20例患者；在此，我们报告一例新病例，一名2.5岁女性，是[基因名称]中一个移码变异和一个错义变异的复合杂合子。她的临床表现与中度表型一致，证实了[基因名称]变异的类型和致病机制与相关表型严重程度之间的直接相关性。
