下颌骨肢端发育不良合并早衰的LMNA基因突变研究  

Mutation analysis of the LMNA gene in a child with mandibuloacral dysplasia and progeria

作　　者：阳芳 李乾 刘宝华 黄家敏 姜北雪 梅忠喜 廖梦思 石莉 张倩倩 YANG Fang;LI Qian;LIU Bao-hua;HUANG Jia-min;JIANG Bei-xuel;MEI Zhong-xi;LIAO Meng-si;SHI Li;ZHANG Qian-qian(Department of Dermatology,Shenzhen People's Hospital/the Second Clinical Medical College,Ji'nan University/the First Affiliated Hospital,Southern University of Science and Technology,Shenzhen 518020,China;National Research Institute for Family Planning,Bejing 100081,China;Shenzhen Univerisity,Health Science Center School of Basic Medical Sciences,Shenzhen 518073,China)

机构地区：[1]深圳市人民医院/暨南大学第二临床医学院/南方科技大学第一附属医院皮肤科,广东深圳518020 [2]国家卫生健康委科学技术研究所,北京100081 [3]深圳大学医学部基础医学院,广东深圳518073

出　　处：《临床皮肤科杂志》2023年第1期7-10,共4页Journal of Clinical Dermatology

摘　　要：目的:报告1例下颌骨肢端发育不良合并早衰患者,并进行分子遗传学诊断。方法:提取1例早老外貌患儿及其父亲外周血DNA。对LMNA基因外显子和侧翼序列进行测序,并以150例无关系健康人作为对照。结果:患者男,7岁。生长迟滞,脱发,骨骼畸形伴脂肪萎缩7年。患儿头部皮肤菲薄,头皮静脉明显,脂肪萎缩,皮肤有斑状色素加深,脊柱侧弯畸形,手指挛缩。X线片示指短挛缩,骨质疏松,锁骨缺失。多普勒超声显示双侧颈内动脉走形扭曲旋转。近亲结婚,父母无外观异常。患儿LMINA基因9号外显子c.1579C>T(p.Arg527Cys)纯合点突变(dbSNP:rs57318642),父亲为杂合突变,母亲去世未测。150例健康人对照均未检测到该位点突变。结论:LMNA基因9号外显子c.1579C>T突变为该例下颌骨肢端发育不良合并早衰的发病原因。Objective: A case of a 7-year-old child with mandibuloacral dysplasia(MAD) and progeria, with mutation analysis of the LMNA gene by molecular genetic testing is reported. Methods: Peripheral blood samples were collected from a 7-year-old child with mandibuloacral dysplasia(MAD) and progeria, his father, and 150 unrelated healthy controls, respectively. DNA was extracted from these samples, and PCR was performed to amplify exons of the LMNA gene and its flanking sequence followed by sequencing. Results: The patient presented with a 7-year history of growth impairment, resulting in poor weight gain, short stature and loss of subcutaneous fat, alopecia, as well as skeletal dysplasia. The patient also had thin skin, prominent superficial veins of the scalp, macular hyperpigmentation, scoliosis, and finger joint contractures. The X-ray examination revealed fixed flexion deformities of the phalanges, reduced bone mineral density and loss of clavicles. Doppler sonography revealed tortuous internal carotid artery. The patient had consanguinous parents, who exhibited no symptoms. His mother died of unknown cancer. A homozygous mutation 1579C>T resulted in a missense arginine to cysteine substitution at amino acid position 527 p.Arg527Cyst(dbSNP:rs57318642) in the exon 9 of LMNA in the proband, heterozygous for this variant in his father. No mutation in the LMNA gene was found in the 150 unrelated control individuals. Conclusion: Homozygous mutation 1579C>T in the exon 9 of LMNA gene resulted in MAD and progeria in this patient.

关 键 词：下颌骨肢端发育不良 A型脂肪代谢障碍 早衰 分子诊断技术 LMNA基因 

分 类 号：R758.5[医药卫生—皮肤病学与性病学]