我们介绍了一名男性患者,在妊娠38周出生,四肢根茎缩短,肝肿大,脑室肿大,心力衰竭,左心室功能严重下降,双心室肥大,和双心房扩大。其他身体发现包括肛门前移位,椎骨异常,短柄。病人的心脏畸形导致持续性低血压,窦性心动过速,在没有心律失常的情况下多器官衰竭。在生命日(DOL)8订购快速全外显子组测序。病人的家人选择撤回支持治疗,那天晚上他就去世了.全外显子组测序在死后返回并在NAA10、E100K中鉴定出变体。基因型表型最接近奥格登综合征或氨基末端乙酰转移酶缺乏症。这种罕见的X连锁综合征的典型特征包括早衰症状,未能茁壮成长,发育迟缓,低张力,和心律失常.其他家庭成员进行了测试,病人的母亲,有轻度智力残疾史的人,以及后来出生的女儿,被确定为携带者。所有携带者均未发现心脏。携带者姐妹表现为发育迟缓和皮质萎缩。蛋白质建模,进化,动力学,人口变异评估,和免疫沉淀描述了NAA10与NAA15相互作用的变体的有害性质。这些发现对索引患者的死后诊断具有后续意义。对于女性携带者来说,关于计划生育。我们强调,当治疗选择有限时,这些快速基因测试和变异特征如何可能导致医疗保健提供者和危重或致命疾病患者的家庭成员之间做出明智的决策。
We present a male patient born at 38-wk gestation with rhizomelic shortening of extremities, hepatomegaly, ventriculomegaly, heart failure, severely depressed left ventricular function, biventricular hypertrophy, and biatrial enlargement. Additional physical findings included anteriorly displaced anus, vertebral anomalies, and brachydactyly. The patient\'s cardiac malformations led to persistent hypotension, sinus tachycardia, and multiorgan failure in the absence of arrhythmias. Rapid whole-exome sequencing was ordered on day of life (DOL) 8. The patient\'s family elected to withdraw supportive care, and he passed away that evening. Whole-exome sequencing returned posthumously and identified a variant in NAA10, E100K. The genotype-phenotype was closest to Ogden syndrome or amino-terminal acetyltransferase deficiency. Typical features of this rare X-linked syndrome include progeroid appearance, failure to thrive, developmental delays, hypotonia, and cardiac arrhythmias. Other family members were tested and the patient\'s mother, who has a history of mild intellectual disability, as well as a daughter born later, were identified as carriers. All carriers showed no cardiac findings. The carrier sister has manifested developmental delay and cortical atrophy. Protein modeling, evolution, dynamics, population variant assessments, and immunoprecipitation depict the deleterious nature of the variant on the interactions of NAA10 with NAA15 These findings had subsequent implications for posthumous diagnosis of the index patient, for female carriers, and regarding family planning. We highlight how these rapid genetic tests and variant characterization can potentially lead to informed decision-making between health-care providers and family members of patients with critical or lethal conditions when treatment options are limited.