KMT2A基因新发突变导致Wiedemann-Steiner综合征合并矮身材1例
A Case of Wiedemann-Steiner Syndrome with Short Stature Caused by a Novel Mutation in KMT2A Gene
DOI: 10.12677/ACM.2021.117422, PDF,  被引量    科研立项经费支持
作者: 马 岭, 徐庆吉：平邑县中医院儿科，山东 临沂；胡艳艳*：临沂市人民医院儿科，山东 临沂
关键词: Wiedemann-Steiner综合征；KMT2A基因；矮身材；重组人生长激素；Wiedemann-Steiner Syndrome； KMT2A Gene； Short Stature； Recombinant Human Growth Hormone
摘要: 目的：探讨1例KMT2A基因新发突变导致的Wiedemann-Steiner综合征(WDSTS)合并矮身材患儿的临床特点和重组人生长激素(rhGH)治疗效果。方法：收集1例WDSTS患儿的临床资料，进行全外显子基因测序，应用rhGH治疗，并进行文献复习。结果：患儿女，6岁7个月，因“生长迟缓6年”就诊，身高109.0 cm (−2.01 SD)，头围47.0 cm (< −2.0 SD)，浓眉，眼距宽，眼睑下垂，宽鼻梁，牙列不整齐，牙齿间距宽，指趾短，颈背部、前臂、下肢多毛，基因检测显示患儿KMT2A基因第16号外显子存在新发杂合突变，变异位点c.5005-2A>G，患儿父母无此变异。给予rhGH治疗3月，身高增长3.0 cm，治疗过程中未出现不良反应。结论：WDSTS合并矮身材患儿短期应用rhGH治疗有效，远期需要监测其安全性。
Abstract: Objective: To investigate the clinical characteristics and therapeutic effect of recombinant human growth hormone (rhGH) in a case of Wiedemann-Steiner syndrome (WDSTS) with short stature caused by a novel mutation of KMT2A gene. Methods: The clinical data of a child with WDSTS were collected, the whole exon gene was sequenced, rhGH was used, and the literature was reviewed. Results: The child aged 6 years and 7 months whose chief complaint was growth retardation for 6 years. Her height was 109.0 cm (−2.01 SD), and head circumference was 47.0 cm (< −2.0 SD). She showed thick eyebrow, wide distance between eyes, ptosis, wide nasal bridge, irregular dentition, wide distance between teeth, short fingers and toes, hairy neck, back, forearm and lower limbs. Gene testing showed that there was a new heterozygous mutation in exon 16 of KMT2A gene, mutation site is c.5005-2A>G. There was no variation in this site in her parents. After rhGH treatment for 3 months, her height increased by 3.0 cm, and there was no adverse reaction during the treatment. Conclusion: Short-term rhGH therapy is effective in children with WDSTS and short stature, and long-term safety monitoring is needed.
文章引用：马岭, 徐庆吉, 胡艳艳. KMT2A基因新发突变导致Wiedemann-Steiner综合征合并矮身材1例[J]. 临床医学进展, 2021, 11(7): 2914-2919. https://doi.org/10.12677/ACM.2021.117422

参考文献

[1] Wiedemann, H.R., Kunze, J., Grosse, F.R., et al. (1989) A Syndrome of Abnormal Facies, Short Stature, and Psychomotor Retardation. Atlas of Clinical Syndromes: A Visual Aid to Diagnosis for Clinicians and Practicing Physicians, 198-199.
[2] Steiner, C.E. and Marques, A.P. (2000) Growth Deficiency, Mental Retardation and Unusual Facies. Clinical Dysmorphology, 9, 155-156. [Google Scholar] [CrossRef] [PubMed]
[3] Jones, W.D., Dafou, D., McEntagart, M., et al. (2012) De Novo Mutations in MLL Cause Wiedemann-Steiner Syndrome. The American Journal of Human Genetics, 91, 358-364. [Google Scholar] [CrossRef] [PubMed]
[4] 上官华坤, 胡旭昀, 沈亦平, 等. KMT2A基因新突变导致Wiedemann-Steiner综合征1例并文献复习[J]. 中华内分泌代谢杂志, 2019, 35(1): 26-31.
[5] Fontana, P., Passaretti, F.F., Maioli, M., et al. (2020) Clinical and Molecular Spectrum of Wiedemann-Steiner Syndrome, an Emerging Member of the Chromatinopathy Family. World Journal of Medical Genetics, 9, 1-11. [Google Scholar] [CrossRef] 
[6] Milne, T.A., Briggs, S.D., Brock, H.W., et al. (2002) MLL Targets SET Domain Methyltransferase Activity to Hox Gene Promoters. Molecular Cell, 10, 1107-1117. [Google Scholar] [CrossRef] [PubMed]
[7] Zhu, J., Sammons, M.A., Donahue, G., et al. (2015) Gain-of-Function p53 Mutants Co-Opt Chromatin Pathways to Drive Cancer Growth. Nature, 525, 206-211. [Google Scholar] [CrossRef] [PubMed]
[8] Li, N., Wang, Y., Yang, Y., et al. (2018) Description of the Molecular and Phenotypic Spectrum of Wiedemann-Steiner Syndrome in Chinese Patients. Orphanet Journal of Rare Diseases, 13, Article No. 178. [Google Scholar] [CrossRef] [PubMed]
[9] Baer, S., Afenjar, A., Smol, T., et al. (2018) Wiedemann-Steiner Syndrome as a Major Cause of Syndromic Intellectual Disability: A Study of 33 French Cases. Clinical Genetics, 94, 141-152. [Google Scholar] [CrossRef] [PubMed]
[10] Stoyle, G., Banka, S., Langley, C., et al. (2018) Growth Hormone Deficiency as a Cause for Short Stature in Wiedemann-Steiner Syndrome. Endocrinology, Diabetes & Metabolism Case Reports, 2018, 1-4. [Google Scholar] [CrossRef] 
[11] Faundes, V., Newman, W.G., Bernardini, L., et al. (2018) Histone Lysine Methylases and Demethylases in the Landscape of Human Developmental Disorders. The American Journal of Human Genetics, 102, 175-187. [Google Scholar] [CrossRef] [PubMed]
[12] Schott, D.A., Gerver, W.J.M. and Stumpel, C.T.R.M. (2017) Growth Hormone Therapy in Children with Kabuki Syndrome: 1-Year Treatment Results. Hormone Research in Paediatrics, 88, 258-264. [Google Scholar] [CrossRef] [PubMed]
[13] Sun, Y., Hu, G., Liu, H., et al. (2017) Further Delineation of the Phenotype of Truncating KMT2A Mutations: The Extended Wiedemann-Steiner Syndrome. American Journal of Medical Genetics A, 173, 510-514. [Google Scholar] [CrossRef] [PubMed]
[14] Liu, J.X., Liang, S.M., Xue, M., et al. (2020) Wiedemann-Steiner Syndrome with a De Novo Mutation in KMT2A: A Case Report. Medicine (Baltimore), 99, e19813. [Google Scholar] [CrossRef] 

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