Department of Clinical Genetics, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
Department of Neurology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
J Peripher Nerv Syst. 2017 Dec;22(4):464-467. doi: 10.1111/jns.12236. Epub 2017 Sep 11.
We report a family in which an autosomal dominantly inherited Charcot-Marie-Tooth (CMT) disease type 2 was suspected. The affected family members (proband, sister, father, and paternal aunt) showed intrafamilial clinical variability. The proband needed walking aids since adolescence because of generalized muscle weakness. The sister showed the same symptoms although to a lesser extent. The father and paternal aunt had foot deformity and atrophy of lower legs. A homozygous GDAP1 mutation was found in the proband and in the sister. Further testing showed compound heterozygous GDAP1 mutations in the father and paternal aunt. In this CMT2 family with a pseudodominant inheritance pattern DNA-diagnostics revealed the presence of both homozygous and compound heterozygous GDAP1 mutations. We recommend including multiple family members in genetic studies on CMT families.
我们报告了一个常染色体显性遗传的 Charcot-Marie-Tooth（CMT）疾病 2 型家族，该家族疑似存在这种疾病。受影响的家族成员（先证者、姐姐、父亲和姑母）表现出家族内临床变异性。先证者由于全身肌肉无力，从青春期开始就需要助行器。姐姐也有同样的症状，只是程度较轻。父亲和姑母则有足部畸形和小腿萎缩。先证者和姐姐均发现 GDAP1 基因突变呈纯合子。进一步的检测显示，父亲和姑母均存在 GDAP1 基因突变的复合杂合子。在这个具有拟显性遗传模式的 CMT2 家族中，DNA 诊断显示存在 GDAP1 基因突变的纯合子和复合杂合子。我们建议在 CMT 家族的遗传研究中纳入多个家族成员。
