Schneider C, Ziegler A, Ricker K, Grimm T, Kress W, Reimers C D, Meinck H, Reiners K, Toyka K V
Department of Neurology, University of Würzburg, Germany.
Neurology. 2000 Aug 8;55(3):383-8. doi: 10.1212/wnl.55.3.383.
To investigate anticipation in proximal myotonic myopathy (PROMM).
PROMM is a recently described autosomal dominantly inherited disorder similar to but distinct from myotonic dystrophy (DM). DM belongs to the group of inherited disorders with anticipation caused by an unstable trinucleotide repeat expansion. In PROMM, no mutation has been identified, although PROMM has recently been mapped to a gene locus on chromosome 3q.
We investigated 10 German families with the PROMM phenotype and linkage to chromosome 3q. We based our analysis of anticipation on the age of disease onset. Anticipation was assumed if the offspring had first symptoms earlier in life than his or her affected parent. For statistical analysis Independence Estimating Equations (IEE) and a Monte-Carlo bootstrap were used.
In 27 affected living parent-offspring pairs from these 10 families, the mean difference of disease onset was 18.8 years with either statistical analysis (p < 10-14 and p < 10-15). The mean disease onset interval in years was greater in father-offspring as compared to the mother-offspring pairs (p < 0.05; IEE).
Our findings suggest the occurrence of anticipation in parent-offspring pairs from families with the PROMM phenotype and linkage to chromosome 3q. The different disease onset intervals in mother-offspring and father-offspring pairs could indicate a mild parent-of-origin effect. These observations are compatible with the suggestion that PROMM, like DM, may be a trinucleotide repeat associated disorder. In contrast to DM, anticipation in PROMM is milder, a congenital form does not seem to occur, and fertility does not appear to be affected.
研究近端肌强直性肌病（PROMM）中的遗传早现现象。
PROMM是一种最近描述的常染色体显性遗传疾病，与强直性肌营养不良（DM）相似但又有所不同。DM属于由不稳定三核苷酸重复序列扩增导致遗传早现的遗传性疾病组。在PROMM中，虽然最近已将其定位到3号染色体q臂上的一个基因座，但尚未鉴定出突变。
我们研究了10个具有PROMM表型且与3号染色体q臂连锁的德国家庭。我们基于疾病发病年龄对遗传早现进行分析。如果后代出现首发症状的年龄比其患病父母更早，则认为存在遗传早现。统计分析采用独立估计方程（IEE）和蒙特卡罗自抽样法。
在这10个家庭的27对健在的患病亲子对中，无论采用哪种统计分析方法，疾病发病的平均差异均为18.8岁（p < 10-14和p < 10-15）。与母子对相比，父子对中疾病发病间隔的平均年数更大（p < 0.05；IEE）。
我们的研究结果表明，具有PROMM表型且与3号染色体q臂连锁的家庭中，亲子对之间存在遗传早现现象。母子对和父子对中不同的疾病发病间隔可能表明存在轻微的亲本效应。这些观察结果与PROMM可能像DM一样是一种三核苷酸重复相关疾病的观点相符。与DM不同的是，PROMM中的遗传早现现象较轻，似乎不会出现先天性形式，且生育能力似乎未受影响。
