A novel mutation and a known mutation in the CLCN7 gene associated with relatively stable infantile malignant osteopetrosis in a Chinese patient
A novel mutation and a known mutation in the CLCN7 gene associated with relatively stable infantile malignant osteopetrosis in a Chinese patient
复制标题
CLCN7 基因中的一个新突变和一个已知突变与中国患者相对稳定的婴儿恶性骨石症相关。
DOI：
10.1016/j.gene.2015.10.021
复制
发表时间：
2016-01-15
期刊：
影响因子：
3.5
通讯作者：
Wang, Yiming
中科院分区：
文献类型：
--
作者：
Zeng, Binghui;Li, Ru;Wang, Yiming
骨质疏松症是一组由破骨细胞功能障碍引起的异质性疾病。CLCN7和TCIRG1基因是导致婴儿恶性骨质疏松症（IMO）的主要专性基因。IMO患者通常在婴儿期或三岁前死亡。在这项研究中，我们报告了一位在7个月大时被诊断为IMO的患者。患者表现为IMO的典型放射学特征。她还表现出红细胞减少、血小板减少、肝脾肿大和神经变性。父母停止了对病人的任何治疗。令人惊讶的是，患者在4岁零9个月时第二次入院时，尽管在未经治疗期间没有得到任何医疗支持，但病情并未恶化。我们对患者及其父母的CLCN7和TCIRG1基因进行了测序，发现了一种新的c.285+1G> a （IVS3+1G> a）突变和一种已知的c.896C>T （p.A1a299Val）突变。新的c.285+1G>突变发生在CLCN7的第三个内含子的剪接供体上。预计该突变会干扰外显子3和4之间的正常剪接，从而从C端截断711个氨基酸，导致编码蛋白的所有功能域丢失。c.896C >t （p.A1a299Val）突变是先前已知的致病突变。我们未发现TCIRG1基因的任何致病性突变。众所周知，clcn7相关的骨质疏松症具有很高的表型异质性。我们的研究表明，在表型进展中存在广泛的异质性，并扩大了CLCN7基因的突变谱。(C) 2015 Elsevier B.V.版权所有
Osteopetrosis is a group of heterogeneous disorders caused by the dysfunction of osteoclasts. The CLCN7 and TCIRG1 genes are the major obligate genes responsible for infantile malignant osteopetrosis (IMO). IMO patients usually die in infancy or before three years of age. In this study, we report a patient who was diagnosed with IMO at seven months of age. The patient presented with classical radiological features of IMO. She also exhibited erythropenia, thrombocytopenia, hepatosplenomegaly and neurodegeneration. The parents discontinued any medical treatment for the patient. Surprisingly, the patient's condition did not deteriorate when she was admitted a second time at the age of four years and nine months, despite not receiving any medical support during the untreated period. We sequenced the CLCN7 and TCIRG1 genes of the patient and her parents and identified a novel c.285+1G>A (IVS3+1G>A) mutation and the known c.896C>T (p.A1a299Val) mutation. The novel c.285+1G>A mutation occurred on the splice donor of the third intron of CLCN7. This mutation was predicted to interfere with normal splicing between exons 3 and 4, thereby truncating 711 amino acids from the C terminus and resulting in the loss of all of the functional domains of the encoded protein. The c.896C>T (p.A1a299Val) mutation was a previously known pathogenic mutation. We did not find any pathogenic mutations in the TCIRG1 gene. CLCN7-related osteopetrosis is known to have a high phenotype heterogeneity. Our study demonstrates a wide heterogeneity in the progression of the phenotypes and expanded the mutational spectrum for the CLCN7 gene. (C) 2015 Elsevier B.V. All rights reserved.