Harada Daisuke, Yamanaka Yoshitaka, Ueda Koso, Shimizu Junya, Inoue Masaru, Seino Yoshiki, Tanaka Hiroyuki
Department of Pediatrics, Okayama University Graduated School of Medicine and Dentistry, Okayama 700-8558, Japan.
Bone. 2005 Feb;36(2):317-22. doi: 10.1016/j.bone.2004.08.005.
Cartilage-hair hypoplasia (CHH) is an autosomal recessive metaphyseal chondrodysplasia characterized by severe short-limb short stature and hypoplastic hair. The responsible gene for CHH has been identified to be ribonuclease of mitochondrial RNA-processing (RMRP) gene. We examined RMRP genes of a 3-year-old Japanese CHH boy and his family and revealed a novel mutation: 20 bp duplication (TACTCTGTGAAGCTGAGGAC), in promoter region of maternal allele, at nucleotide -3 and a reported 218A>G point mutation in transcribed region of paternal allele. No treatment for CHH has been established so far. Growth hormone (GH) action has its effect on linear growth and on bone remodeling and homeostasis. Recently, GH has been used to improve severe short stature caused by not only GH deficiency (GHD) but also some skeletal dysplasias including achondroplasia. To improve severe short stature, we treated the patient with 0.175 mg kg-1 week-1 of GH for 7 years. His height was improved from -4.2 SD to -3.0 SD by 1 year of GH treatment. Following treatment had given positive effects continuously on his height to -2.6 SD by 3.1 years GH medication. Then, when he was 6 years old, surgical lengthening was performed and his height reached to -2.0 SD. After the surgery, we continued GH treatment. Additional GH treatment of 3.6 more years had kept his height to -2.0 SD. However, when he was 8 years old, because there was an interruption of GH treatment, the velocity of his height was obviously decreased comparing before and during the interruption, which was calculated 3.4 and 2.2 cm/year, respectively, and the SD score was decreased to -2.1 SD. This result of total 7 years of GH treatment suggested that GH treatment significantly improved his disturbed bone growth and had also positive efficacy to keep growth rate. This result implies the connection between GH signal and RMRP gene. Additionally, GH may be considered to be an efficient treatment for CHH.
软骨毛发发育不全（CHH）是一种常染色体隐性遗传的干骺端软骨发育不良，其特征为严重的短肢矮小症和毛发发育不全。已确定CHH的致病基因是线粒体RNA加工核糖核酸酶（RMRP）基因。我们检测了一名3岁日本CHH男孩及其家族的RMRP基因，发现了一个新的突变：母本等位基因启动子区域核苷酸-3处有20bp重复（TACTCTGTGAAGCTGAGGAC），父本等位基因转录区域有一个已报道的218A>G点突变。目前尚未确立CHH的治疗方法。生长激素（GH）作用于线性生长以及骨骼重塑和内稳态。最近，GH已被用于改善不仅由生长激素缺乏症（GHD）引起的严重矮小症，还包括软骨发育不全等一些骨骼发育异常导致的矮小症。为改善严重矮小症，我们以0.175mg·kg-1·周-1的剂量对该患者进行了7年的GH治疗。GH治疗1年后，他的身高从-4.2标准差提高到了-3.0标准差。持续治疗3.
