Immunodeficiency in a patient with microcephalic osteodysplastic primordial dwarfism type I as compared to Roifman syndrome
Immunodeficiency in a patient with microcephalic osteodysplastic primordial dwarfism type I as compared to Roifman syndrome
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DOI：
10.1016/j.braindev.2020.09.007
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发表时间：
2021-01-07
影响因子：
1.7
通讯作者：
Nonoyama, Shigeaki
中科院分区：
文献类型：
--
作者：
Hagiwara, Hidetoshi;Matsumoto, Hiroshi;Nonoyama, Shigeaki
背景：小头性骨增生异常原发性侏儒症I型（MOPD I，也称为Taybi-Linder综合征）是一种罕见的遗传性疾病，与严重的宫内发育迟缓、身材矮小、小头畸形、脑异常、四肢发育迟缓和早期死亡相关。导致这种疾病的基因RNU4ATAC不编码蛋白质，而是编码U4atac小核RNA (snRNA)，这是小剪接体的重要组成部分。Roifman综合征是一种以免疫缺陷并发症为特征的MOPD I的等位基因疾病。病例报告：患者是一名18岁的女性，表现为先天性侏儒症和小头畸形，伴有结构性脑异常。她在一岁时患有人类疱疹病毒6 （HHV-6）相关的急性坏死性脑病，此后导致严重的精神运动障碍。使用基因微阵列和全外显子组测序的遗传分析无法确定其先天性异常的原因。然而，Sanger测序显示RNU4ATAC （NR_023343.1:n）中存在复合杂合突变。[50g > a]；[55g > a])。免疫学结果显示总淋巴细胞、CD4(+) T细胞和T细胞再生活性降低。此外，对水痘带状疱疹、风疹、麻疹、腮腺炎和流感的抗体非常低或阴性，尽管接种了这些病毒的疫苗。HHV-6 IgG抗体也未检出。讨论：该患者表现出明显的MOPD I表型并伴有各种免疫缺陷。先前的研究并未证实MOPD I患者存在免疫缺陷合并症，但本报告提示MOPD I患者存在明显的免疫缺陷。(C) 2020日本儿童神经病学学会。Elsevier B.V.版权所有。
Background: Microcephalic osteodysplastic primordial dwarfism type I (MOPD I, also known as Taybi-Linder syndrome) is a rare genetic disorder associated with severe intrauterine growth retardation, short stature, microcephaly, brain anomalies, stunted limbs, and early mortality. RNU4ATAC, the gene responsible for this disorder, does not encode a protein but instead the U4atac small nuclear RNA (snRNA), a crucial component of the minor spliceosome. Roifman syndrome is an allelic disorder of MOPD I that is characterized by immunodeficiency complications.Case report: The patient described herein is an 18-year-old woman exhibiting congenital dwarfism and microcephaly with structural brain anomaly. She suffered human herpesvirus 6 (HHV-6)-associated acute necrotizing encephalopathy at the age of one, thereafter resulting in severe psychomotor disabilities. Genetic analysis using gene microarray and whole-exome sequencing could not identify the cause of her congenital anomalies. However, Sanger sequencing revealed a compound heterozygous mutation within RNU4ATAC (NR_023343.1:n.[50G > A];[55G > A]). Immunological findings showed decreases in total lymphocytes, CD4(+) T cells, and T cell regenerative activity. Furthermore, antibodies against varicella-zoster, rubella, measles, mumps, and influenza were very low or negative despite having received vaccinations for these viruses. HHV-6 IgG antibodies were also undetected.Discussion: The patient here exhibited a marked MOPD I phenotype complicated by various immunodeficiencies. Previous studies have not demonstrated immunodeficiency comorbidities within MOPD I subjects, but this report suggests an evident immunodeficiency in MOPD I. Patients with MOPD I should be treated with one of the immunodeficiency syndromes. (C) 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.