Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affliated the Sixth People's Hospital, Shanghai 200233, 600 Yi-Shan Rd., PR China.
Gene. 2013 May 25;521(1):191-4. doi: 10.1016/j.gene.2013.03.047. Epub 2013 Mar 24.
Primary hypertrophic osteoarthropathy (PHO) is a rare monogenetic disease that closely mimics hypertrophic osteoarthropathy secondary to pulmonary or other pathology. The study of PHO provides an opportunity to understand both the pathogenesis of hypertrophic osteoarthropathy and the functions of the underlying genes. PHO is characterized by digital clubbing, periostosis and pachydermia. Two genes are known to be related to PHO: SLCO2A1 and HPGD. Here, we identified a recurrent heterozygous guanine-to-adenine transition at the invariant +1 position of the donor site of intron 7 (c.940+1G>A) and a novel heterozygous missense mutation p.Asn534Lys (c.1602C>A) in exon 11 of SLCO2A1 in a Chinese young man with PHO. Identification of a novel genotype in PHO will provide clues to the phenotype-genotype relations and may assist not only in the clinical diagnosis of PHO but also in the interpretation of genetic information used for prenatal diagnosis and genetic counseling.
原发性肥大性骨关节病 (PHO) 是一种罕见的单基因疾病,其表现与继发于肺部或其他病变的肥大性骨关节病非常相似。对 PHO 的研究为了解肥大性骨关节病的发病机制和潜在基因的功能提供了机会。PHO 的特征是指端杵状畸形、骨膜增生和厚皮症。有两种基因与 PHO 有关:SLCO2A1 和 HPGD。在这里,我们在中国一位患有 PHO 的年轻男性中发现了 SLCO2A1 第 7 内含子供体位点不变的 +1 位置上的杂合性鸟嘌呤到腺嘌呤的反复转换(c.940+1G>A)和第 11 外显子上的新型杂合性错义突变 p.Asn534Lys(c.1602C>A)。在 PHO 中发现新的基因型将为表型-基因型关系提供线索,不仅有助于 PHO 的临床诊断,也有助于解释用于产前诊断和遗传咨询的遗传信息。