Case report: Novel compound heterozygous missense mutations in the DDHD2 gene in a Chinese patient associated with spastic paraplegia type 54.
Case report: Novel compound heterozygous missense mutations in the DDHD2 gene in a Chinese patient associated with spastic paraplegia type 54.
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DOI：
10.3389/fped.2022.997274
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发表时间：
2022
影响因子：
2.6
通讯作者：
Tang, Jian
中科院分区：
文献类型：
--
作者：
Xu, Xin;Lu, Fen;Du, Senjie;Zhao, Xiaoke;Li, Hongying;Zhang, Li;Tang, Jian
54 型痉挛性截瘫 (SPG54) 是一种罕见的遗传性常染色体隐性遗传疾病，也是一种由磷脂酶 DDHD2 基因突变引起的复杂的遗传性痉挛性截瘫 (HSP)。 SPG54的特点是早发痉挛性截瘫、智力障碍和胼胝体发育不良。我们报道了一名 9 岁零 5 个月的中国女孩，患有进行性下肢痉挛、肌肉无力和智力障碍。脑磁共振成像（MRI）显示脑室周围白质软化和胼胝体变薄。根据韦克斯勒智力量表，她的智商为 42。通过全外显子组测序，在先证者中鉴定出 DDHD2 基因 [c.168G>C, p.(Trp56Cys) 和 c.1505T>C, p.(Phe502Ser)] 中的新型复合杂合错义突变。不同物种的氨基酸序列比对表明，DDHD2 蛋白中的 Trp56 和 Phe502 在进化过程中高度保守。多种计算机预测工具表明这两种突变都是有害的。我们的研究报告了一个非常罕见的复杂 HSP 病例，该病例是由 DDHD2 基因中两种新型复合杂合突变引起的。我们的发现扩大了 SPG54 的遗传谱。
Spastic paraplegia type 54 (SPG54) is a rare inherited autosomal recessive disorder, and a complex hereditary spastic paraplegia (HSP) caused by mutations in the phospholipase DDHD2 gene. SPG54 is characterized by early onset of spastic paraplegia, intellectual disability and dysplasia of corpus callosum. We report a 9 years and 5 months old Chinese girl with progressive spasm of the lower limbs, muscle weakness and intellectual disability. Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia and thinning of the corpus callosum. According to the Wechsler Intelligence Scale, her IQ is 42. By whole exome sequencing, novel compound heterozygous missense mutations in the DDHD2 gene [c.168G>C, p.(Trp56Cys) and c.1505T>C, p.(Phe502Ser)] were identified in the proband. Comparative amino acid sequence alignment across different species revealed that Trp56 and Phe502 in the DDHD2 protein were highly conserved during evolution. And multiple in silico prediction tools suggested that both mutations were deleterious. Our study reports a very rare case of complicated HSP caused by two novel compound heterozygous mutations in the DDHD2 gene. Our findings expand the genetic spectrum of SPG54.
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影响因子：
6
作者：
Nicita, Francesco;Stregapede, Fabrizia;Travaglini, Lorena
通讯作者：
Travaglini, Lorena
DOI：
10.1073/pnas.1413706111
发表时间：
2014-10-14
影响因子：
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作者：
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通讯作者：
de Brouwer, Arjan P. M.
影响因子：
9.8
作者：
Schuurs-Hoeijmakers, Janneke H. M.;Geraghty, Michael T.;de Brouwer, Arjan P. M.
通讯作者：
de Brouwer, Arjan P. M.