Two different genetic etiologies for tuberous sclerosis complex (TSC) in a single family.
Two different genetic etiologies for tuberous sclerosis complex (TSC) in a single family.
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一个家族中有两种不同的结节性硬化症 (TSC) 遗传病因。
DOI：
10.1002/mgg3.1296
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发表时间：
2020
影响因子：
2
通讯作者：
Northrup,Hope
中科院分区：
文献类型：
--
作者：
Mowrey,Kate;Koenig,MaryKay;Szabo,CharlesA;Samuels,Joshua;Mulligan,Shannon;Pearson,DeborahA;Northrup,Hope
研究背景多发性硬化症（TSC）是一种常染色体显性遗传疾病，涉及皮肤异常、心脏、大脑和肾脏的错构瘤、癫痫发作以及TSC相关神经精神疾病（TAND）。约90%-95%的TSC患者在TSC 1或TSC 2中存在可识别的致病性变异。我们在这里提出了两个家庭成员与TSC的临床诊断，后来确定是由于两种不同的遗传病因。MethodsA 2岁的白人女性（患者1）出生于非血缘健康的父母，并确定有TSC的临床诊断在2个月大。她的叔祖父（患者2）也已知有TSC的临床诊断。测序和缺失/重复分析for TSC 1和TSC 2上进行两个individual.ResultsMutation分析显示，患者1和患者2有可识别的致病性变异在TSC 2。患者1有c.4800_4801delTG（p.Cys1600Trpfs*2），而患者2有c.4470_4471delinsTT（p.Glu1490_Lys1491delinsAsp*）.ConclusionTo our knowledge，our clinical report is of significant as it is the third kind to be identified with affected members with two distinct genetic etiologies for TSC.我们的病例报告强调了将基因检测纳入具有TSC特征的个体的临床评估的重要性。
BackgroundTuberous sclerosis complex (TSC) is an autosomal dominant genetic condition that involves abnormalities of the skin, hamartomas in the heart, brain, and kidneys, seizures, as well as TSC‐associated neuropsychiatric disorders (TAND). About 90%–95% of individuals with TSC will have an identifiable pathogenic variant in eitherTSC1orTSC2. We present here two family members with clinical diagnoses of TSC that were later determined to be due to two different genetic etiologies.MethodsA 2‐year‐old Caucasian female (Patient 1) was born to non‐consanguineous healthy parents and was determined to have a clinical diagnosis of TSC at 2 months old. Her paternal great‐uncle (Patient 2) was also known to have a clinical diagnosis of TSC. Sequencing and deletion/duplication analysis forTSC1andTSC2were performed on both individuals.ResultsMutation analysis revealed that both Patient 1 and Patient 2 had identifiable pathogenic variants inTSC2. Patient 1 had c.4800_4801delTG (p.Cys1600Trpfs*2), while Patient 2 had c.4470_4471delinsTT (p.Glu1490_Lys1491delinsAsp*).ConclusionTo our knowledge, our clinical report is of significance as it is the third kindred to be identified with affected members with two distinct genetic etiologies for TSC. Our case report highlights the importance of incorporating genetic testing into the clinical evaluation for individuals with features suggestive of TSC.