Satoh Chisei, Kondoh Tatsuro, Shimizu Hitomi, Kinoshita Akira, Mishima Hiroyuki, Nishimura Gen, Miyazaki Mutsuko, Okano Kunihiko, Kumai Yoshihiko, Yoshiura Koh-Ichiro
Department of Otolaryngology-Head and Neck Surgery, Unit of Translation Medicine, Japan; Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Division of Developmental Disabilities, Misakaenosono Mutsumi Developmental, Medical and Welfare Center, Isahaya, Japan.
Eur J Med Genet. 2021 Feb;64(2):104125. doi: 10.1016/j.ejmg.2020.104125. Epub 2020 Dec 25.
COL27A1 encodes a collagen type XXVII alpha 1 chain. It is the product of this gene that provides the structural support of connective tissue and is reported to be the causative gene of Steel syndrome (OMIM #615155). The primary symptoms of patients with this defect are consistent with systemic bone disease; however, recent reports note findings of intellectual disability and hearing loss. In this study, we identified novel COL27A1 compound heterozygous variants in two brothers with rhizomelia and congenital hip dislocation as well as dental and genital abnormalities that have not yet been reported in Steel syndrome. This variant, of maternal origin, caused an amino acid substitution of arginine for glycine, c.2026G>C or p.G676R, in the collagen helix domain, which is assumed to damage the structure of the helix. The paternally transmitted variant, c.2367G>A, is located at the 3' end of exon 12, and cDNA analysis revealed a splicing alteration. These novel, compound heterozygous COL27A1 variants might indicate an association of the gene with tooth and genital abnormalities.
COL27A1基因编码一种XXVII型胶原蛋白α1链。正是该基因的产物为结缔组织提供结构支撑，据报道它是斯蒂尔综合征（OMIM #615155）的致病基因。患有这种缺陷的患者的主要症状与全身性骨病一致；然而，最近的报告指出了智力残疾和听力损失的发现。在本研究中，我们在两名患有肢根短小和先天性髋关节脱位以及牙齿和生殖器异常的兄弟中鉴定出了新的COL27A1复合杂合变异体，这些异常在斯蒂尔综合征中尚未见报道。这种源自母亲的变异体在胶原蛋白螺旋结构域导致了甘氨酸被精氨酸取代，即c.2026G>C或p.G676R，这被认为会破坏螺旋结构。父系遗传的变异体c.2367G>A位于外显子12的3'端，cDNA分析显示存在剪接改变。这些新的复合杂合COL27A1变异体可能表明该基因与牙齿和生殖器异常有关。
