一例以性发育迟缓、身材矮小为表现的Pol III相关性脑白质营养不良病例报道
Case Report: Pol III-Related Leukodystrophy with Developmental Delay and Short Stature
DOI: 10.12677/ACM.2024.142431, PDF,   
作者: 周姝君：青岛大学附属青岛市海慈医院(青岛市中医医院)，山东 青岛；胡思翠：青岛大学附属妇女儿童医院，山东 青岛
关键词: POLR3A；脑白质营养不良；低促性腺激素；矮小症；POLR3A； Leukodystrophy； Hypogonadotropin； Short Stature
摘要: 本文报告1例POLR3A突变导致性发育迟缓、矮小病例。患儿为15岁女性，表现为性发育迟缓、身材矮小、牙齿稀疏，后发际线低，颈短，颈璞。其父母为近亲。MR提示脑白质髓鞘化明显落后。全外显子组测试显示POLR3A存在一个新的纯合变异c.3226G > A，该变异导致该患者POLR3A的低髓鞘型脑白质营养不良。本病以对症支持治疗为主。本文通过对该病例的报告，期望提高对该疾病的认识。
Abstract: This article reports a case of developmental delay and short stature caused by a mutation in the POLR3A gene. The patient is a 15-year-old female presenting with delayed sexual development, short stature, sparse teeth, low posterior hairline, short neck, and webbed neck. The parents are consanguineous. Magnetic resonance imaging (MRI) indicates significant hypomyelination in the brain white matter. Whole-exome sequencing revealed a novel homozygous variant, c.3226G > A, in the POLR3A gene, resulting in hypomyelinating leukodystrophy in this patient. The management of this condition primarily involves symptomatic and supportive treatment. This case report aims to enhance awareness and understanding of this disorder through the presentation of the described case.
文章引用：周姝君, 胡思翠. 一例以性发育迟缓、身材矮小为表现的Pol III相关性脑白质营养不良病例报道[J]. 临床医学进展, 2024, 14(2): 3045-3049. https://doi.org/10.12677/ACM.2024.142431

参考文献

[1] Bernard, G., Chouery, E., Putorti, M.L., et al. (2011) Mutations of POLR3A Encoding a Catalytic Subunit of RNA Polymerase Pol III Cause a Recessive Hypomyelinating Leukodystrophy. The American Journal of Human Genetics, 89, 415-423. [Google Scholar] [CrossRef] [PubMed]
[2] Tétreault, M., Choquet, K., Orcesi, S., et al. (2011) Re-cessive Mutations in POLR3B, Encoding the Second Largest Subunit of Pol III, Cause a Rare Hypomyelinating Leu-kodystrophy. The American Journal of Human Genetics, 89, 652-655. [Google Scholar] [CrossRef] [PubMed]
[3] Thiffault, I., Wolf, N.I., Forget, D., et al. (2015) Recessive Muta-tions in POLR1C Cause a Leukodystrophy by Impairing Biogenesis of RNA Polymerase III. Nature Communications, 6, Article Number: 7623. [Google Scholar] [CrossRef] [PubMed]
[4] Dorboz, I., Dumay-Odelot, H., Boussaid, K., et al. (2018) Mutation in POLR3K Causes Hypomyelinating Leukodystrophy and Abnormal Ribosomal RNA Regulation. Neurology Genetics, 4, e289. [Google Scholar] [CrossRef] 
[5] Watt, K.E., Macintosh, J., Bernard, G. and Trainor, P.A. (2023) RNA Polymerases I and III in Development and Disease. Seminars in Cell & Developmental Biology, 136, 49-63. [Google Scholar] [CrossRef] [PubMed]
[6] Ashrafi, M.R., Amanat, M., Garshasbi, M., et al. (2020) An Update on Clinical, Pathological, Diagnostic, and Therapeutic Perspectives of Childhood Leukodystrophies. Expert Re-view of Neurotherapeutics, 20, 65-84. [Google Scholar] [CrossRef] [PubMed]
[7] Minnerop, M., Kurzwelly, D., Wagner, H., et al. (2017) Hypomorphic Mutations in POLR3A Are a Frequent Cause of Sporadic and Recessive Spastic Ataxia. Brain, 140, 1561-1578.
[8] Vanderver, A., Tonduti, D., Bernard, G., et al. (2013) More than Hypomyelination in Pol-III Disorder. Journal of Neuropathology & Experimental Neurology, 72, 67-75. [Google Scholar] [CrossRef] 
[9] 梁超, 陆海英, 郭虎. 4H综合征的临床表现与分子诊断(附1例报告) [J]. 临床神经病学杂志, 2017, 30(5): 377-379.
[10] 宋小珍, 张育才, 陈育才, 等. 3例4H综合征新基因突变与临床表型研究[C]//中国生物物理学会临床分子诊断分会, 中国遗传学会遗传诊断分会. 第一届中国临床分子诊断大会论文集. 上海: 中国生物物理学会临床分子诊断分会, 中国遗传学会遗传诊断分会, 2018.
[11] 李玲, 朱泽宇, 曹立, 等. 中年女性, 进行性走路困难35年余——POLR3A基因复合杂合突变致HLD7 [J]. 中国神经精神疾病杂志, 2022, 48(3): 188-192.
[12] Wu, S., Bai, Z., Dong, X., et al. (2019) Novel Mutations of the POLR3A Gene Caused POLR3-Related Leukodystrophy in a Chinese Family: A Case Report. BMC Pediatrics, 19, Ar-ticle Number: 289. [Google Scholar] [CrossRef] [PubMed]
[13] Yang, H., Wu, Z., Li, X., et al. (2023) A Novel Variant of the POLR3A Gene in a Chinese Patient with POLR3-Related Leukodystrophy. Neurological Sciences, 44, 3363-3368. [Google Scholar] [CrossRef] [PubMed]
[14] Minnerop, M., Kurzwelly, D., Wagner, H., et al. (2017) Hypo-morphic Mutations in POLR3A Are a Frequent Cause of Sporadic and Recessive Spastic Ataxia. Brain, 140, 1561-1578.
[15] Neocleous, V., Fanis, P., Toumba, M., et al. (2020) GnRH Deficient Patients with Congenital Hy-pogonadotropic Hypogonadism: Novel Genetic Findings in ANOS1, RNF216, WDR11, FGFR1, CHD7, and POLR3A Genes in a Case Series and Review of the Literature. Frontiers in Endocrinology (Lausanne), 11, 626. [Google Scholar] [CrossRef] [PubMed]
[16] Bernard, G. and Vanderver, A. (2012) POLR3-Related Leu-kodystrophy. In: Adam, M.P., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., Amemiya, A., Eds., University of Washington, Seattle, WA, 1993-2023.
[17] Kevelam, S.H., Steenweg, M.E., Srivastava, S., et al. (2016) Update on Leukodystrophies: A Historical Perspective and Adapted Definition. Neuropediatrics, 47, 349-354. [Google Scholar] [CrossRef] [PubMed]

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