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伴有或不伴有脉络膜视网膜病变、淋巴水肿或智力发育迟缓的小头畸形与KIF11致病变异相关:病例报告及基因型-表型相关性分析

Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation associated with KIF11 pathogenic variant: case report and genotype-phenotype correlation analysis.

作者信息

Peng Jiajia, Xie Yan, Wang Hui, Huang Lijuan, Yang Yangfan, Li Ningdong

机构信息

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Sun Yat-sen University, Sun Yat-Sen University Zhongshan Ophthalmic Center, Guangzhou, 510060, Guangdong, China.

Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.

出版信息

BMC Ophthalmol. 2025 Jul 30;25(1):437. doi: 10.1186/s12886-025-04261-y.

Abstract

BACKGROUND

Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) is a rare autosomal dominant disease caused by variants in the gene. Additionally, recent advances in genetic testing have led to the increasing identification of gene variants in FEVR patients. Harboring similar point variants in the gene, patients exhibit striking variability in clinical manifestations. However, comprehensive clinical characterization of MCLMR patients with variants are only mentioned by a few case reports and the genotypic and phenotypic variability in -associated disease was not thoroughly investigated. Therefore, one case is discussed alongside a systematic review of published MCLMR cases to clarify genotype-phenotype correlations.

CASE PRESENTATION

An 8-year-old boy was referred to our clinic due to poor vision. Clinical evaluation revealed microcephaly, characteristic chorioretinopathy and mild developmental delay, in the absence of primary lymphedema. Additional findings included special facial features, bilateral simian crease and metabolic abnormalities featuring elevated urine glucose and ketone bodies despite normoglycemia. Brain magnetic resonance imaging (MRI) demonstrated microcephaly with simplified gyration, delayed myelination, and cortical thickening. Whole exome sequencing (WES) identified a previously reported synonymous variant in (c.2922G > A, p.Pro974=), which was confirmed and co-segregated by Sanger sequencing.

CONCLUSIONS

A Chinese boy was diagnosed with MCLMR following the identification of a pathogenic gene point variant, as classified according to ACMG guidelines. Combined with previously reported literature, a total of 55 pathogenic variants have been identified, distributed throughout the entire gene. A recurrent mutational hotspot (c.1159 C > T, p.Arg238*) was observed. Additionally, frameshift and splicing variants collectively account for over 50% of cases. Notably, missense variants are associated with more severe phenotypic manifestations, suggesting a genotype-phenotype correlation. This case, supported by comprehensive clinical data, contributes to a more complete elucidation of the phenotypic spectrum of -related disorders.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s12886-025-04261-y.

摘要

背景

伴或不伴有脉络膜视网膜病变、淋巴水肿或智力发育迟缓的小头畸形(MCLMR)是一种由该基因变异引起的罕见常染色体显性疾病。此外,基因检测的最新进展导致在家族性渗出性玻璃体视网膜病变(FEVR)患者中越来越多地发现该基因变异。携带该基因类似点变异的患者临床表现差异显著。然而,仅有少数病例报告提及了具有该变异的MCLMR患者的全面临床特征,且与该基因相关疾病的基因型和表型变异性尚未得到充分研究。因此,本文讨论了1例病例,并对已发表的MCLMR病例进行了系统综述,以阐明基因型与表型的相关性。

病例介绍

一名8岁男孩因视力差转诊至我院。临床评估发现小头畸形、特征性脉络膜视网膜病变和轻度发育迟缓,无原发性淋巴水肿。其他发现包括特殊面容、双侧猿掌纹以及尽管血糖正常但尿糖和酮体升高的代谢异常。脑磁共振成像(MRI)显示小头畸形伴脑回简化、髓鞘形成延迟和皮质增厚。全外显子测序(WES)鉴定出该基因中一个先前报道的同义变异(c.2922G>A,p.Pro974=),经桑格测序证实并共分离。

结论

一名中国男孩在鉴定出一个致病性该基因点变异后被诊断为MCLMR,该变异根据美国医学遗传学与基因组学学会(ACMG)指南进行分类。结合先前报道的文献,共鉴定出55个致病性该基因变异,分布于整个基因。观察到一个复发性突变热点(c.1159 C>T,p.Arg238*)。此外,移码和剪接变异共占病例的50%以上。值得注意的是,错义变异与更严重的表型表现相关,提示基因型与表型的相关性。该病例得到全面临床数据的支持,有助于更完整地阐明与该基因相关疾病的表型谱。

补充信息

在线版本包含可在10.1186/s12886-025-04261-y获取的补充材料。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee85/12312374/81c8d17d06ff/12886_2025_4261_Fig1_HTML.jpg

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