Heiman Paige, Drewes Sarah, Ghaloul-Gonzalez Lina
Division of Medical Genetics, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
SAGE Open Med Case Rep. 2021 Feb 1;9:2050313X21990982. doi: 10.1177/2050313X21990982. eCollection 2021.
Variants in CAMK2-associated genes have recently been implicated in neurodevelopmental disorders and intellectual disability. The clinical manifestations reported in patients with mutations in these genes include intellectual disability (ranging from mild to severe), global developmental delay, seizures, delayed speech, behavioral abnormalities, hypotonia, episodic ataxia, progressive cerebellar atrophy, visual impairments, and gastrointestinal issues. Phenotypic heterogeneity has been postulated. We present a child with neurodevelopmental disorder caused by a pathogenic variant inherited from a healthy mother. A more mildly affected sib was determined to have the same variant. Monoallelic mutations in in patients have previously only been reported as de novo mutations. This report adds to the clinical phenotypic spectrum of the disease and demonstrates intrafamilial variability of expression of a mutation.
钙调蛋白激酶2（CAMK2）相关基因的变异最近被认为与神经发育障碍和智力残疾有关。这些基因突变患者报告的临床表现包括智力残疾（从轻度到重度）、全面发育迟缓、癫痫发作、语言发育迟缓、行为异常、肌张力减退、发作性共济失调、进行性小脑萎缩、视力障碍和胃肠道问题。已推测存在表型异质性。我们报告一名患有神经发育障碍的儿童，其致病变异遗传自健康母亲。确定一名症状较轻的同胞也有相同变异。此前，患者中的单等位基因突变仅作为新发突变被报道。本报告扩展了该疾病的临床表型谱，并证明了突变表达的家族内变异性。
