CTSK基因突变导致致密性成骨不全症一家系研究

Pycnodysostosis caused by CTSK mutation:one pedigree study

本研究分析由于组织蛋白酶K(cathepsin K, CTSK)基因突变导致的致密性成骨不全症一先证者及其家系成员的临床特征,旨在提高对该罕见病的认识。该家系先证者为8岁男性,非近亲婚配后代,身高116.6 cm(-2SD),牙列紊乱,胫骨骨折2次,全身骨骼密度升高,全外显子组测序和Sanger测序证实其携带CTSK基因复合杂合突变,其中位于5号外显子的杂合错义突变(c.440C>T)为新生突变,导致p.Ala147Val(A147V),另一个位于6号外显子的缺失突变(c.778delA)遗传自先证者父亲,导致p.Ser260AlafsX15;先证者母亲及妹妹未携带上述突变。临床上,致密性成骨不全症需与石骨症和其他类型的骨硬化症鉴别。

The purpose of this study was to analyze the clinical characteristics of a patient with pycnodysostosis caused by cathepsin K(CTSK)gene mutation and his family members in order to improve the understanding of this rare diseases. A pediatric patient with pycnodysostosis was referred to us when he was eight years old. He presented with elevated bone mineral density, short stature, dentition abnormality and multiple fractures of right tibia. Next generation sequencing(NGS)and Sanger sequencing confirmed that the proband carried compound heterozygous mutations of CTSKgene, including a missense mutation c. 440C>T in exon 5(p.Ala147Val)and a deletion mutation c. 778delA in exon 6(p.Ser260AlafsX15)which was inherited from his father. His mother and sister did not carry the above variations. Clinically, it is necessary to differentiate pycnodysostosis from osteopetrosis and other osteosclerotic diseases.