【摘要】 目的 探讨先天性肌强直一家系的临床特点及CLCN1基因突变情况。方法 对一先天性肌强直家系中的22例患者的临床资料进行分析。结果 该家系5代68名成员,连续4代共24例发病,男女均有累及;多于婴幼儿期起病,肌强直见于所有患者,16例伴有肌肥大。全部患者肌酶学检查及血电解质正常;2例肌电图检查见自发性肌强直电位;先证者肌活检见肌纤维排列疏松,大小不一,横纹不清,部分肌纤维增生与肥大,肌细胞轻度变性,周围有少量炎性细胞浸润;3例基因检测未发现CLCN1基因的23对外显子突变。结论 该家系为常染色体显性遗传的Thomsen病,患者均有典型的临床表现。CLCN1基因23对外显子筛查未发现突变,表明可能存在遗传异质性。
【关键词】 先天性肌强直;临床特征; 基因突变
Clinical festures and CLCN1 gene mutation screen on a myotonia congenital kindred
WANG Haizhen,LI Zengfu, ZHENG Hong, et al.
Department of Neurology, the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052, China
Abstract:Objective To investigate the clinical festures and CLCN1 gene mutation screen on a myotonia congenital kindred.Methods The clinical data of 22 patients in the myotonia congenital kindred were analysed. Results There were total 68 people in 5 generations, including 24 patients in 4 generations .Both male and female were suffered. All patientes of this kindred showed myotonia with onset the illness from the infant, and 16 cases accompanied with hypermyotrophy.The levels of creatases and dielectric in serum were normal in all the cases. Spontaneous myotonic electric potential were observed on electromyography( EMG ) in 2 cases.The proband was found in light microscope by biopsy that muscle fibers arranged loosenly , size of them mismatched , transverse striation was unclear and some of them was hyperplasia and hypertrophy. Muscle cells degenerated gently with a few inflammatory cells infiltration. No mutation was found in the whole 23 extrons of CLCN1 gene in the 3 patients.Conclusions This kindred accords with the autosomal dominant heredity form Thomsens disease. The affected numbers have the typical clinical characteristics. No mutation is found when 23 extrons of CLCN1 gene screened in the patients which indicate the genetic heterogeneity may be exist in this kindred.
Key words:myotonia congenital; clinical characteristics;gene mutation
先天性肌强直具有两种遗传类型:常染色体显性遗传的Thomsen病及常染色体隐性遗传的Becker病,均表现为幼年起病的肌强直与运动笨拙。通过对大量家系及散发病例CLCN1基因筛选,发现了许多突变位点与单核苷酸多态性位点。突变散在分布于23个外显子中,无高发热区,给基因突变的寻找工作带来难度。国内目前仅有几个家系报道[1],现将我省2004年10月发现的一先天性肌强直家系5代68名成员中24例患者发病情况、临床特点及基因分析结果报告如下。
1 临床资料
1.1 一般资料 该家系5代共68名成员,患者24例,目前生存22例,2例年长者死于其他疾病,连续4 代均有发病,男女均累及,家系谱图见图1。肌强直见于所有患者,多为出生后不久啼哭时难以睁开眼睛,握拳后手久久不能松开而被发现。随年龄增长出现活动困难或笨拙,尤以动作启动时明显,肌肉僵硬、放松困难,上述情况在紧张、受到刺激或寒冷时易被诱发和加重,温暖或反复运动可减轻。成年后病情渐趋于稳定,一般不影响寿命。肌强直症状波及全身骨骼肌,所有病例均无呼吸肌、吞咽肌、括约肌受累。先证者曾服用苯妥英钠等稳定细胞膜的药物,症状稍有好转。查体均未见肌肉萎缩,16例出现肌肥大,多见于四肢肌如前臂肌、三角肌、腓肠肌等。所有病例叩击肌肉时,出现肌球及局部凹陷,可持续10 s以上,其中11例在舌部出现叩击性肌球。肌力全部为Ⅴ级,余神经系统检查无阳性体征发现。
1.2 实验室检查 (1)肌酶学:22例患者行血清肌酶学检查,包括肌酸激酶(CK)、CK同工酶(CKMB)、乳酸脱氢酶(LDH)、天冬氨酸转氨酶(AST),其中20例全部正常,1例CK 362U/L(20~22 U/L),1例LDH 265 U/L(75~240 U/L)。(2)电解质:22例血钾、钠、氯、钙均在正常范围。(3)肌电图:2例行拇对掌肌、肱二头肌肌电图检查,肌肉松弛时插入针电极见自发性肌强直电位,提插针、叩击肌腹、机械刺激肌肉或随意运动均可诱发,呈现为轰炸机俯冲声音。
1.3 肌活检病理检查 先证者肌活检,HE染色光镜下可见肌束边界清楚,部分肌纤维排列疏松,大小不一,横纹不清,肌纤维部分增生与肥大,肌细胞有轻度变性,周围有少量炎性细胞浸润。
1.4 基因分析 选取家系中3例患者(Ⅱ5、Ⅲ15、Ⅳ4),采用聚合酶链单链构相基因多态性分析(PCRSSCP)方法对CLCN1的23对外显子筛查,未发现基因突变。
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