The third case of Marbach‐Rustad progeroid syndrome caused by a de novo LEMD2 variant
The third case of Marbach‐Rustad progeroid syndrome caused by a de novo LEMD2 variant
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第三例由 LEMD2 新变异引起的 Marbach-Rustad 早衰综合症
DOI：
10.1111/cge.14441
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发表时间：
2023
影响因子：
3.5
通讯作者：
Yunting Lin
中科院分区：
文献类型：
--
作者：
Zhikun Lu;Wen Zhang;X. Mao;Duan Li;Xiao;Li Liu;Yunting Lin
马尔巴赫-鲁斯塔德早老样综合征是一种由LEMD 2基因杂合变异引起的极其罕见的疾病。迄今为止，在马尔巴赫-鲁斯塔德早老样综合征中仅报告了2例患者和1例LEMD 2致病变异。在此，我们描述了全球第三例马尔巴赫-鲁斯塔德早老样综合征，这也是中国首例。先证者患有早产、发育不良、面部畸形、喂养困难、颅骨缺陷和运动里程碑延迟，但智力和言语正常。全外显子组测序（WES）最初在先证者1岁时未发现导致表型的变异。4年后对WES数据的再分析显示，先证者在LEMD 2基因中携带一种新生杂合c.1436 C>T（p.Ser479 Phe）变异，已知该变异导致马尔巴赫-鲁斯塔德类早衰综合征。桑格测序证实了先证者存在这种变异，而他的父母和两个姐妹篇不存在这种变异。我们的研究为先证者提供了准确的临床诊断，并增加了一名新的马尔巴赫-鲁斯塔德早老样综合征患者。我们的研究表明LEMD 2 c.1436C>T（p.Ser479Phe）变异体是一个热点。我们的工作也表明，WES数据的阴性病例的重新分析可能会发现致病性变异，提高诊断效率。
Marbach‐Rustad progeroid syndrome is an extremely rare disease caused by a heterozygous variant in the LEMD2 gene. To date, only two patients and one LEMD2 pathogenic variant have been reported in Marbach‐Rustad progeroid syndrome. Here we describe the third case of Marbach‐Rustad progeroid syndrome worldwide, which is also the first case in China. The proband was affected with premature birth, failed to thrive, facial abnormalities, feeding difficulties, skull defects and delayed motor milestones, but had a normal intelligence and speech. Whole exome sequencing (WES) initially did not find a phenotype‐causing variant when the proband was 1 year of age. The reanalysis of WES data 4 years later revealed the proband harbored a de novo heterozygous c.1436C>T(p.Ser479Phe) variant in the LEMD2 gene, which is known responsible for Marbach‐Rustad progeroid syndrome. Sanger sequencing confirmed the presence of this variant in the proband and absence in his parents and two elder sisters. Our study provides accurate clinical diagnosis for the proband and adds a new patient with Marbach‐Rustad progeroid syndrome. Our study suggests the LEMD2 c.1436C>T(p.Ser479Phe) variant as a hotspot. Our work also indicates reanalysis of WES data of negative cases might identify pathogenic variant and improve diagnostic efficiency.
影响因子：
7.2
作者：
Worman, Howard J.;Ostlund, Cecilia;Wang, Yuexia
通讯作者：
Wang, Yuexia