Cheema Asma Naseer, Shi Ruyu, Kamboh M Ilyas
Children's Hospital & The Institute of Child Health Multan, Multan 66000, Pakistan.
Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Int J Mol Sci. 2025 Jan 3;26(1):352. doi: 10.3390/ijms26010352.
A couple presented to the office with an apparently healthy infant for a thorough clinical assessment, as they had previously lost two male children to a neurodegenerative disorder. They also reported the death of a male cousin abroad with a comparable condition. We aimed to evaluate a novel coding pathogenic variant c.1097T>A, , within the affected family, previously identified in a deceased cousin, but its clinical significance remained undetermined. A 200 bp PCR product of target genome (including codon 366 of ) was amplified followed by enzymatic digestion (I) and sequencing. Structural pathogenic variant analysis was performed using PyMOL 2.5.4. In RFLP analysis, the mutant-type allele produced a single band of 200 bp, and the wild-type allele manifested as two bands of 112 bp and 88 bp. The pathogenic variant was identified in nine family members, including two heterozygous couples with consanguineous marriages resulting in affected children. It was predicted to be deleterious by multiple bioinformatic tools. The substitution of nonpolar isoleucine with polar asparagine of iPLA2 (Ile366Asn) resulted in a eense pathogenic variant (ATC>AAC). A missense variant (p. Ile366Asn) in the gene is associated with clinically evident infantile neuroaxonal dystrophy, which is transmitted in an autosomal recessive pattern, and is also predicted to be dysfunctional by bioinformatic analyses.
一对夫妇带着一个看似健康的婴儿前来诊所进行全面的临床评估，因为他们之前有两个男孩死于一种神经退行性疾病。他们还报告说，在国外有一个患有类似疾病的男性表亲去世。我们旨在评估一个新的编码致病变体c.1097T>A，该变体在一个受影响的家族中被发现，之前在一个已故的表亲身上也有发现，但其临床意义仍未确定。对目标基因组的200 bp PCR产物（包括[相关基因]的第366密码子）进行扩增，随后进行酶切（I）和测序。使用PyMOL 2.5.4进行结构致病变体分析。在RFLP分析中，突变型等位基因产生一条200 bp的单带，野生型等位基因表现为两条分别为112 bp和88 bp的带。在9名家庭成员中鉴定出了该致病变体，其中包括两对近亲结婚的杂合夫妇，他们的孩子受到了影响。多种生物信息学工具预测该变体具有有害性。iPLA2的非极性异亮氨酸被极性天冬酰胺取代（Ile366Asn）导致了一个错义致病变体（ATC>AAC）。[相关基因]中的一个错义变体（p. Ile366Asn）与临床上明显的婴儿神经轴索营养不良相关，该病以常染色体隐性模式遗传，并且生物信息学分析也预测该变体功能失调。
