摘要
目的调查2例以不明原因杵状指趾为主要表现的儿童患者的临床特点,并对患者及其家系进行致病基因突变研究。方法纳入2例以杵状指趾为主要表现的女性患儿,详细询问病史,评估患者骨骼影像学特点,测量骨代谢生化指标及骨密度,筛查杵状指趾相关的继发原因,采用Sanger直接测序法检测HPGD基因突变。结果先证者及其妹妹均在出生6个月后逐渐出现杵状指趾及掌跖多汗,先证者有先天性动脉导管未闭病史。两例患者均无面部皮肤增厚及关节肿胀,X线片未见骨膜增厚等异常表现。2例患者骨吸收指标和骨密度在性别、年龄匹配的正常范围,临床未检出导致杵状指趾的其他疾病。基因检测提示两患者存在HPGD基因第3外显子c.310_311del CT和第3内含子c.324+5G>A的复合杂合突变,其父母亲分别为上述突变的携带者,提示患儿罹患原发性肥厚性骨关节病(primary hypertrophic osteoarthropathy,PHO)。结论PHO为罕见的遗传性疾病,常呈常染色体隐性遗传,女性患者可能表现不典型,疾病早期可仅有杵状指趾的表现,容易漏诊。检测HPGD等PHO致病基因突变,有助于提高PHO的诊断水平。
Objective To investigate the phenotypes of two girls with main manifestation of unexplained digital clubbing and to detecte its pathogenic mutations in their family. Methods Two girls who suffered from digital clubbing were included. Clinical features, serum levels of bone turnover biomarkers, bone radiography, and bone mineral density （BMD） were evaluated. Secondary causes of digital clubbing were screened. Sanger sequencing was performed to detect mutation in HPGD gene in these patients and their parents. Results The proband and her sister suffered from digital clubbing, palmar and plantar hyperhidrosis since 6-month-old. The proband had a medical history of patent ductus arterio-sus. Pachydermia and joint swelling were not found in 2 patients. X-ray films did not show signs of pachydermia. Bone re-sorption biomarker and BMD were in age and gender matched normal range. Secondary causes of digital clubbing were not identified. The compound heterozygous mutations of c. 310_ 311delCT in exon 3 and c. 324＋5G〉A in intron 3 were identified in the patients, and their parents were heterozygous carriers. It suggested that the diagnosis of these two patients was primary hypertrophic osteoarthropathy （PHO）. Conclusions PHO is a rare genetic disease, usually inherited as an autosomal recessive trait. Clinical presentations in females were untypical. They could present with isolated digital clubbing at early stage of the disease. Detection of the mutations in HPGD and other pathogenic genes of PHO would improve the diagnosis of PHO.
作者
吕芳
宋玉文
李路娇
王鸥
姜艳
夏维波
邢小平
李梅
LYU Fang;SONG Yu-wen;LI Lu-jiao;WANG Ou;JIANG Yan;XIA Wei-bo;XING Xiao-ping;LI Mei(Department of Endocrinology, Peking U）lion Medical College Hospital, Chinese Academy of Medical Sciences ＆ Peking U）lion Medical College, Key Laboratory of Endocrinology, National Heahh Commission, Beijing 100730, China)
出处
《中华骨质疏松和骨矿盐疾病杂志》
CSCD
北大核心
2018年第3期240-247,共8页
Chinese Journal Of Osteoporosis And Bone Mineral Research
基金
国家自然科学基金面上项目(81570802)
中国医学科学院医学与健康科技创新工程项目(2016-I2M-3-003)
国家重点研发计划(2016YFC0901501)
