Identification of a novel compound heterozygous mutation and a homozygous mutation of SLURP1 in Chinese families with Mal de Meleda.
Identification of a novel compound heterozygous mutation and a homozygous mutation of SLURP1 in Chinese families with Mal de Meleda.
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DOI：
10.1186/s12920-023-01580-1
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发表时间：
2023-07-01
影响因子：
2.7
通讯作者：
中科院分区：
文献类型：
--
作者：
Mal de Meleda是一种常染色体隐性掌跖角化病，SLURP 1被确定为致病基因。虽然已经报道了超过20个SLURP 1突变，但在中国患者中仅检测到c.256G > A（p.G87R）突变。在这里，我们报告了一个新的杂合SLURP 1突变的中国家庭。我们评估了2例中国梅勒达病患者的临床表现，并从患者和其他家庭成员中收集标本进行全外显子组和桑格测序。我们使用算法（MutationTaster、SIFT、PolyPhen-2、PROVEAN、PANTHER、FATHMM、mCSM、SDM和DUET）来预测检测到的突变的致病潜力。我们还使用AlphaFold 2和PyMOL进行蛋白质结构分析。两例患者均表现为掌跖角化病的典型表现。在先证者1中，我们检测到SLURP 1外显子3的一个新的复合杂合突变（c.243C > A和c.256G > A）。先证者2为一个近亲家庭的成年女性，携带纯合突变（c.211C > T）。算法表明这两种突变可能是致病的。我们使用AlphaFold 2来预测这些突变的蛋白质结构，并发现它们会导致不稳定性，如PyMOL所示。我们的研究发现了一个新的复合杂合突变（c.243C > A和c.256G > A），在中国患者与Mal de Meleda，有可能导致蛋白质结构的不稳定性。此外，这项研究扩展了SLURP 1突变的现有知识，并有助于了解Mal de Meleda。在线版本包含补充材料，可通过10.1186/s12920-023-01580-1获得。
Mal de Meleda is an autosomal recessive palmoplantar keratoderma, with SLURP1 identified as the pathogenic gene responsible. Although over 20 mutations in SLURP1 have been reported, only the mutation c.256G > A (p.G87R) has been detected in Chinese patients. Here, we report a novel heterozygous SLURP1 mutation in a Chinese family. We assessed the clinical manifestations of two Chinese patients with Mal de Meleda and collected specimens from the patients and other family members for whole-exome and Sanger sequencing. We used algorithms (MutationTaster, SIFT, PolyPhen-2, PROVEAN, PANTHER, FATHMM, mCSM, SDM and DUET) to predict the pathogenetic potential of the mutation detected. We also employed AlphaFold2 and PyMOL for protein structure analysis. Both patients displayed the typical manifestation of palmoplantar keratoderma. In Proband 1, we detected a novel compound heterozygous mutation (c.243C > A and c.256G > A) in exon 3 of SLURP1. Proband 2 was an adult female born to a consanguineous family and carried a homozygous mutation (c.211C > T). Algorithms indicated both mutations to be probably disease causing. We used AlphaFold2 to predict the protein structure of these mutations and found that they cause instability, as shown by PyMOL. Our study identified a novel compound heterozygous mutation (c.243C > A and c.256G > A) in a Chinese patient with Mal de Meleda that has the potential to cause instability in protein structure. Moreover, this study expands on the existing knowledge of SLURP1 mutations and contributes to knowledge of Mal de Meleda. The online version contains supplementary material available at 10.1186/s12920-023-01580-1.
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影响因子：
16.6
作者：
Bryant P;Pozzati G;Elofsson A
通讯作者：
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