KIF11基因变异致小头畸形伴或不伴脉络膜视网膜病变、淋巴水肿或智力障碍综合征眼部临床特征分析  

Analysis of ocular clinical features of KIF1l mutation induced microcephaly with or without chorioretinopathy,lymphedema,or intellectual disability syndrome

作　　者：史丽英 卢跃兵 孙爽[1] 徐利辉 刘婷[1] 白大勇[2] 孙先桃 Shi Liying;Lu Yuebing;Sun Shuang;Xu Lihui;Liu Ting;Bai Dayong;Sun Xiantao(Department of Ophthalmology,Children's Hospital Afiliated to Zhengzhou University,Henan Children's Hospital,Zhengzhou Children's Hospital,Zhengzhou 450018,China;Department of Ophthalmology,Bejing Children's Hospital,National Center for Children's Health,Capital Medical University,Beijing 100045,China)

机构地区：[1]郑州大学附属儿童医院,河南省儿童医院郑州儿童医院眼科,郑州450018 [2]首都医科大学附属北京儿童医院眼科,北京100045

出　　处：《中华眼底病杂志》2024年第11期825-832,共8页Chinese Journal of Ocular Fundus Diseases

基　　金：郑州市科技惠民计划项目(2021KJHM0011);河南省医学科技攻关计划(联合共建)项目(LHGJ20220716)。

摘　　要：目的观察并分析常染色体显性遗传性小头畸形伴或不伴脉络膜视网膜病变、淋巴水肿或智力障碍综合征(MCLMR)患儿的临床特点。方法回顾性临床研究。2023年9月于河南省儿童医院眼科检查并经基因检测确诊的MCLMR一家系(先证者及其3名家系成员)纳入研究。采集临床资料,详细询问病史及家族史,并行最佳矫正视力(BCVA)、光相干断层扫描(OCT)、荧光素眼底血管造影(FFA)、闪光视觉诱发电位(F-VEP)、全视野视网膜电图(ERG)以及头颅核磁共振成像(MRI)和全身系统性检查。采集先证者及其父母、胞弟外周静脉血3 ml,提取全基因组DNA。采用二代测序技术进行基因测序。对于可疑致病变异位点,通过Sanger测序进行验证,生物信息学分析确定基因变异位点的致病性。计算机检索美国国立医学图书馆医学数据库PubMed、万方数据库相关文献。总结遗传学特点,并进行文献复习。结果先证者(Ⅱ-1),女,8岁5个月。头颅偏小,下颌较小,耳朵突出,鼻头宽,睑裂向上倾斜,人中长。轻度智力发育迟缓,无淋巴水肿病史。右眼、左眼BCVA分别为0.08、0.1。双眼眼球震颤。双眼黄斑区及下方脉络膜视网膜萎缩性病灶。FFA检查,黄斑区及下方视网膜斑驳样荧光着染,晚期无明显荧光素渗漏。OCT检查,黄斑中心凹形态浅,椭圆体带缺失,层次欠清楚,视网膜全层变薄,黄斑下方脉络膜视网膜全层明显萎缩。F-VEP检查,双眼未引出波形。全视野ERG检查,双眼a、b波振幅重度降低。头颅MRI检查,左侧颞部蛛网膜下腔增宽,脑实质内未见明显异常信号。其父亲(Ⅰ-1)轻度眼球震颤、斜视;母亲(Ⅰ-2)、胞弟(Ⅱ-2)眼部表型未见明显异常。基因检测结果显示,先证者(Ⅱ-1)KIF11基因第8号外显子存在c.895A>G(p.Ile299Val)杂合错义变异,为已知变异。其父母(Ⅰ-1、Ⅰ-2)、胞弟(Ⅱ-2)均为野生型。生物信息学分析结果显示,该变异为可能�ObjectiveeTo observe and analyze the clinical characteristics of children with autosomal dominant hereditary microcephaly with or without chorioretinopathy,lymphedema,or intellectual disability syndrome(MCLMR).Methods A retrospective clinical study.In September 2023,the first patient and three family members(parents,brother)of MCLMR who were diagnosed through ophthalmic examination and genetic testing at Department of Ophthalmology of Henan Children's Hospital were included in the study.Clinical data were collected,inquired about medical history and family history in detail,and performed best corrected visual acuity(BCVA),optical coherence tomography(OCT),fluorescein angiography(FFA),flash visual evoked potential(F-VEP),full field electroretinogram(ERG),cranial magnetic resonance imaging(MRI),and systemic examination.3 ml of peripheral venous blood were collected from the proband,her parents and younger brother,and extracted whole genome DNA.Second generation sequencing technology was used for gene sequencing.For suspected pathogenic sites,Sanger sequencing was used for validation,and bioinformatics analysis was performed to determine the pathogenicity of the genetic variant sites.The relevant literature of PubMed of the National Library of Medicine and Wan Fang Med Online by computer were searched.The genetic characteristics and conducted literature review were summarized.Results The proband(II-1)was an 8-year-old and 5-monthold female.Her head was relatively small,the lower jaw was small,the ears protrude,the nose was wide,the eyelid was tilted upwards,philtrum was long.Mild intellectual disability,no history of lymphedema.The BCVA values for the right and left eyes were 0.08 and 0.1,respectively.Bilateral nystagmus.Atrophic lesioned in the macular area and below choroid retina of both eyes.FFA examination showed mottled fluorescent staining in the macular area and the below retina,with no obvious fluorescein leakage in the late stage.OCT examination revealed shallow macular fovea morphology,absence of ellipsoi

关 键 词：脉络膜视网膜病变 KIF11基因 小/头畸形 眼球震颤 

分 类 号：R725.9[医药卫生—儿科] R771.3[医药卫生—临床医学]