Compound heterozygous variants in MAPK8IP3 were detected in severe congenital hypotonia mimicking lethal spinal muscular atrophy.
Compound heterozygous variants in MAPK8IP3 were detected in severe congenital hypotonia mimicking lethal spinal muscular atrophy.
复制标题
在模仿致死性脊髓性肌萎缩症的严重先天性肌张力低下中检测到 MAPK8IP3 的复合杂合变异体。
DOI：
10.1002/ajmg.a.63340
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Morava,Éva
中科院分区：
文献类型：
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作者：
Kárteszi,Judit;Ziegler,Alban;Tihanyi,Mariann;Elmont,Beatrix;Zhang,Yuebo;Patócs,Barbara;Molnár,MáriaJudit;Méhes,Gábor;Wells,Kirsty;Jakus,Rita;Bessenyei,Beáta;Ranatunga,Wasantha;Morava,Éva
丝裂原活化蛋白激酶8相互作用蛋白3基因（MAPK 8IP 3）编码c-Jun-氨基末端激酶相互作用蛋白3（JIP 3），参与轴突逆行转运。MAPK 8IP 3中的杂合从头致病性变体导致神经发育障碍，伴或不伴脑异常和可能的轴突周围神经病变。对表现为神经源性严重先天性肌张力减退（模仿致死性脊髓性肌萎缩）的个体进行全外显子组测序。在MAPK 8IP 3中检测到复合杂合罕见变体（剪接和错义），该变体遗传自健康父母。在肌肉活检样品中的蛋白质印迹分析显示JIP 3表达减少超过60%。在这里，我们提出了一种新的常染色体隐性遗传表型的下运动神经元疾病引起的JIP 3缺陷。
Mitogen‐activated protein kinase 8‐interacting protein 3 gene (MAPK8IP3)encodes the c‐Jun‐amino‐terminal kinase‐interacting protein 3 (JIP3) and is involved in retrograde axonal transport. Heterozygous de novo pathogenic variants inMAPK8IP3result in a neurodevelopmental disorder with or without brain abnormalities and possible axonal peripheral neuropathy. Whole‐exome sequencing was performed on an individual presenting with severe congenital muscle hypotonia of neuronal origin mimicking lethal spinal muscular atrophy. Compound heterozygous rare variants (a splice and a missense) were detected inMAPK8IP3,inherited from the healthy parents. Western blot analysis in a muscle biopsy sample showed a more than 60% decrease in JIP3 expression. Here, we suggest a novel autosomal recessive phenotype of a lower motor neuron disease caused by JIP3 deficiency.