LMNA基因突变致下颌骨锁骨发育不全的临床特征  

Clinical features of mandibuloacral dysplasia caused by LMNA mutation

作　　者：李响 姜艳 王鸥 李梅 邢小平 夏维波 LI Xiang;JIANG Yan;WANG Ou;LI Mei;XING Xiao-ping;XIA Wei-bo(Department of Endocrinology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Key Laboratory of Endocrinology,National Health Commission of the People's Republic of China,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院内分泌科国家卫生和健康委员会内分泌重点实验室

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2019年第4期347-355,共9页Chinese Journal Of Osteoporosis And Bone Mineral Research

摘　　要：目的 报道1例诊断为下颌骨锁骨发育不全(mandibuloacral dysplasia,MAD)的患者,并归纳总结MAD的临床特征以及目前报道的与MAD发病相关的LMNA基因突变位点。方法 对1例MAD患者进行病史采集、体格检查和辅助检查。通过骨病panel测序,并对发现突变的LMNA基因第9外显子进行一代测序验证。检索目前数据库对已报道突变进行总结。结果 患儿,男性,4岁3个月,因“手指杵状改变2年余”于2016年9月就诊。根据患者有锁骨短缩、颅骨畸形、囟门未闭合、身材矮小等表现临床疑诊为颅骨锁骨发育不全,但结合典型的皮肤粗糙、头发稀疏、皮下脂肪萎缩、小颌畸形、皮肤色素沉着、四肢末梢呈杵状、四肢末节骨质溶解等MAD特征,以及基因测序结果,最终诊断为MAD并发A型脂肪代谢障碍。测序发现LMNA第9外显子c.1579C>T和c.1580G>A复合杂合突变,分别导致LMNA基因编码的527位精氨酸错义成半胱氨酸和组氨酸。结论 两处位点的纯合突变病例以往均有报道,c.1579C>T突变表型较重,而该患者临床表现与c.1580G>A突变更相似。总结了LMNA突变致MAD的各突变位点及临床特点,加深了对MAD的认识。Objective To present a case of mandubuloacral dysplasia (MAD), and to review articles to summarize the clinical features and pathogenic LMNA mutations of MAD. Methods We reported the clinical manifestation and auxiliary examination of present patient. By whole exome sequencing, we found a compound heterozygous mutation in LMNA gene. Then we reviewed current reports of MAD and summarized known mutations of LMNA causing MAD. Results A boy aged 4 years and 3 months visited PUMCH because of clubbed fingers, which occurred 2 years ago. As the patient showed shortening clavicles, craniofacial abnormalities, delayed closure of fontanel and short stature, cleidocranial dysplasia (CCD) was suspiciously diagnosed. However, the patient had some different manifestations from CCD, like pachylosis, alopecia, micrognathialy, hyperpigmented skin and acroosteolysis. And gene sequencing showed a compound heterozygous mutation in LMNA gene (c.1579C>T, p.Arg527Cys;c.1580G>A, p.Arg527His). MAD combined with type A lipodystrophy was clear. Conclusion Homozygous mutation of each basic group have been previously reported before. Our patient s manifestation was similar to patients with c.1580G>A mutation, but c.1579C>T mutation could cause severer phenotype. Summarizing mutations in LMNA of MAD and their clinical features deepened our understanding of this rare disease.

关 键 词：下颌骨锁骨发育不全 A型脂肪代谢障碍 LMNA基因 临床特征 

分 类 号：R726[医药卫生—儿科]