摘要目的 分析1个常染色体显性遗传小窝蛋白病(Caveolinopathies)家系的临床特征,进一步行致病基因突变分析,为家系遗传咨询和产前诊断提供依据.方法 收集家系先证者及其他成员的临床资料,提取外周血基因组DNA,应用二代测序技术对先证者进行基因突变分析,并通过一代测序对先证者及家系成员进行突变位点的检测与验证,确定致病突变的类型.结果 先证者表现为儿童期隐匿起病并缓慢进展的四肢远端肌无力与肌萎缩,以双上肢远端为著,伴四肢酸胀感,肌酸激酶中度升高,肌电图提示远端肌呈肌源性损害合并神经源性损害.其大姐、二姐临床症状轻,仅表现为双手轻度萎缩、运动后肌肉酸胀.测序结果显示先证者及其大姐、二姐CAV3基因均存在c.80G＞ A(p.Arg27Gln)杂合突变,该突变为已报道过的致病突变.结论 CA V3基因c.80G＞A(p.Arg27Gln)杂合突变为这个常染色体显性遗传小窝蛋白病家系的致病原因,为家系的遗传咨询和产前诊断提供了依据.

abstractsObjective To analyze clinical features and genetic mutations in a Chinese family affected with autosomal dominant caveolinopathies.Methods Clinical data of the proband and her family members were collected.Genomic DNA was extracted from peripheral blood samples with a standard procedure.Next generation sequencing was carried out for the proband,and direct sequencing was employed to detect potential mutation of the CA V gene.Results The proband presented with slowly progressing distal muscle weakness and atrophy,especially distal upper limbs and muscular soreness during early childhood,with her CK level moderately elevated and EMG showing myogenic and neurogenic injuries.Her sisters presented mild symptoms with hand muscle atrophy and fasciculation after exercise.A heterozygous missense mutation c.80G＞A (p.Arg27Gln),which was reported as being pathogenic,was identified in the CAV3 gene in the proband and her sisters.Conclusion A heterozygous c.80G＞A (p.Arg27Gln) mutation in the CAV3 gene probably underlies the autosomal dominant caveolinopathies in this Chinese family.