HDAC8基因突变所致Cornelia de Lange 综合征1例并文献复习

摘要

<正>Cornelia de Lange综合征（Cornelia de Lange syndrome,CdLS）在1933年由荷兰儿科医生Cornelia首次描述，该病是一种伴有多系统发育异常的遗传缺陷综合征，呈常染色体显性或X连锁显性方式遗传，发病率介于1/10 000～1/30 000活产新生儿，常表现为成比例的身材矮小、宫内及出生后发育迟缓、特定的面部特征、多器官系统畸形（特别是心脏、胃肠道和肌肉骨骼系统）以及认知和行为方面的异常等。该病常见的突变基因有NIPBL、SMC1A、SMC3、RAD21、BRD4、HDAC8和ANKRD11，所有这些基因表达的蛋白都参与组成黏连蛋白复合物或影响其调节功能^[1-2]。本团队对1例CdLS患儿及其家系成员进行基因突变检测，发现患儿携带HDAC8基因c.111+3A>T新发突变，既往未见报道，并统计中国目前报道的HDAC8基因突变所致CdLS患者基因型及临床表现，具体报告如下。

关键词

Cornelia de Lange 综合征 / HDAC8基因 / 突变 / 遗传缺陷综合征

[1] Kline AD, Moss JF, Selicorni A, et al. Diagnosis and management of Cornelia de Lange syndrome: First international consensus statement[J]. Nat Rev Genet, 2018,19(10): 649-666.
[2] Selicorni A, Mariani M, Lettieri A, et al. Cornelia de Lange Syndrome: From a disease to a broader spectrum[J]. Genes (Basel), 2021,12(7):1075.
[3] 马健,张琼琼,张开慧,等. HDAC8基因变异引起新生儿Cornelia de Lange综合征5型一例[J].中华医学遗传学杂志, 2019,36(7): 720-723.
Ma J, Zhang QQ, Zhang KH, et al. Clinical and genetic analysis of a neonate with Cornelia de Lange syndrome 5 caused by HDAC8 gene mutation[J]. Chin J Med Genet, 2019,36(7): 720-723. (in Chinese)
[4] 董燕, 史晓依, 徐瑞娟. HDAC8基因变异所致Cornelia de Lange综合征1例报告[J]. 临床儿科杂志, 2021,39(1): 51-54.
Dong Y, Shi XY, Xu RJ. Cornelia de Lange syndrome caused by HDAC8 gene mutation: A case report[J]. Journal of Clinical Pediatrics, 2021,39(1): 51-54.(in Chinese)
[5] Gao X, Huang Z, Fan Y, et al. A functional mutation in HDAC8 gene as novel diagnostic marker for cornelia de lange syndrome[J]. Cell Physiol Biochem, 2018,47(6): 2388-2395.
[6] Feng L, Zhou D, Zhang Z, et al. Exome sequencing identifies a de novo mutation in HDAC8 associated with Cornelia de Lange syndrome[J]. J Hum Genet, 2014,59(9): 536-539.
[7] Li Q, Chang G, Yin L, et al. Clinical and molecular analysis in a cohort of Chinese children with Cornelia de Lange syndrome[J]. Sci Rep, 2020,10(1): 21224.
[8] Liu C, Li X, Cui J, et al. Analysis of clinical and genetic characteristics in 10 Chinese individuals with Cornelia de Lange syndrome and literature review[J]. Mol Genet Genomic Med, 2020,8(10): e1471.
[9] 赵磊,张庆华,周秉博,等.Cornelia de Lange综合征患儿3例的基因型及表型分析[J].中华医学遗传学杂志, 2023,40(1):7-11.
Zhao L, Zhang QH, Zhou BB, et al. Analysis of genotypes and phenotypes of three children with Cornelia de Lange syndrome[J]. Chin J Med Genet, 2023,40(1): 7-11.(in Chinese)
[10] Yu QX, Jing XY, Lin XM, et al. Fetal phenotype of Cornelia de Lange syndrome with a molecular confirmation[J]. Eur J Obstet Gynecol Reprod Biol, 2023,284: 16-19.
[11] 张孝玲, 黎帆, 吴玫瑰, 等. 新生儿德朗热综合征6例临床特点及基因变异分析[J]. 中华生物医学工程杂志, 2024,30(3): 188-194.
Zhang XL,Li F,Wu MG, et al. Clinical features and gene mutation analysis of 6 newborns with Cornelia de Lange syndrome[J]. Chinese Journal of Biomedical Engineering, 2024,30(3): 188-194.(in Chinese)
[12] Piche J, Van Vliet PP, Puceat M, et al. The expanding phenotypes of cohesinopathies: One ring to rule them all![J]. Cell Cycle, 2019,18(21): 2828-2848.
[13] Shangguan H, Chen R. Phenotypes of Cornelia de Lange syndrome caused by non-cohesion genes: Novel variants and literature review[J]. Front Pediatr, 2022,10: 940294.
[14] Cucco F, Sarogni P, Rossato S, et al. Pathogenic variants in EP300 and ANKRD11 in patients with phenotypes overlapping Cornelia de Lange syndrome[J]. Am J Med Genet A, 2020,182(7): 1690-1696.
[15] Osko JD, Porter NJ, Decroos C, et al. Structural analysis of histone deacetylase 8 mutants associated with Cornelia de Lange syndrome spectrum disorders[J]. J Struct Biol, 2021,213(1): 107681.
[16] Kaur M, Blair J, Devkota B, et al. Genomic analyses in Cornelia de Lange syndrome and related diagnoses: Novel candidate genes, genotype-phenotype correlations and common mechanisms[J]. Am J Med Genet A, 2023,191(8): 2113-2131.
[17] Chhajed M, Lallar M, Gunasekaran PK, et al. A classic Cornelia de Lange syndrome type 5 (CdLS5) with a De novo missense variation of p.Gly210Arg in the HDAC8 gene with a novel phenotype of generalized dystonia[J]. Cureus, 2024,16(5): e60838.
[18] Latorre-Pellicer A, Ascaso A, Trujillano L, et al. Evaluating face2 Gene as a tool to identify cornelia de Lange syndrome by facial phenotypes[J]. Int J Mol Sci, 2020,21(3):1042.
[19] Sarogni P, Pallotta MM, Musio A. Cornelia de Lange syndrome: From molecular diagnosis to therapeutic approach[J]. J Med Genet, 2020,57(5): 289-295.
[20] Boyle MI, Jespersgaard C, Brondum-Nielsen K, et al. Cornelia de Lange syndrome[J]. Clin Genet, 2015,88(1): 1-12.

基金资助

山西省儿童医院(山西省妇幼保健院)院级基金(2021022)