Molecular genetic evidence of clinical heterogeneity in Fukuyama-type congenital muscular dystrophy
Molecular genetic evidence of clinical heterogeneity in Fukuyama-type congenital muscular dystrophy
复制标题
福山型先天性肌营养不良症临床异质性的分子遗传学证据
作者：
E. Kondo;Kayoko Saito;Hajime Tanaka;S. Tsuji;T. Ishihara;M. Ōsawa;Y. Fukuyama;T. Toda
摘要福山型先天性肌营养不良症(FCMD)是一种伴有脑畸形的常染色体隐性遗传性重度肌营养不良症。FCMD的致病基因被定位在染色体9q31上，最近发现了FCMD与mfd220(D9S306)之间存在强连锁不平衡的令人信服的证据。FCMD的临床特征也是运动功能最强，最多允许患者在没有辅助的情况下坐着或在臀部滑动。然而，一小部分患者获得了在没有辅助的情况下行走的能力。这种流动病例是属于FCMD谱系还是属于不同的疾病实体，一直是一个相当有争议的话题。我们使用FCMD基因座两侧的DNA标记对10个流动病例家系进行了连锁分析。Mfd220基因座对动态FCMD的显著Lod评分为3.09。我们还发现了流动的FCMD和mfd220之间连锁不平衡的证据。我们进一步对具有不同表型的FCMD兄弟姐妹进行了单倍型分析，其中一个是流动的，另一个不是。结果表明，在FCMD基因座周围23.3 cM的9个标记基因座上，FCMD同胞具有完全相同的单倍型。在这些结果的基础上，我们得出结论，从遗传学上讲，流动病例实际上是FCMD谱的一部分。
Abstract Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive severe muscular dystrophy associated with brain malformation. The gene responsible for FCMD was mapped to chromosome 9q31, a region in which convincing evidence of strong linkage disequilibrium between FCMD and mfd220 (D9S306) was recently found. FCMD is also characterized clinically by a peak motor function which, at best, allows patients to sit unassisted or slide on the buttocks. However, a small fraction of patients acquire the capacity to walk unassisted. Whether such ambulant cases belong to the FCMD spectrum or to a different disease entity has been a topic of considerable debate. We performed linkage analysis for ten families with ambulant cases using DNA markers flanking the FCMD locus. The mfd220 locus yielded a significant lod score of 3.09 for ambulant FCMD. We also found evidence for linkage disequilibrium between ambulant FCMD and mfd220. We further conducted haplotype analysis in FCMD siblings with different phenotypes, one of whom was ambulant while the other was not. The results indicate that the FCMD siblings share exactly the same haplotype at nine marker loci spanning 23.3 cM surrounding the FCMD locus. On the basis of these results, we conclude that, genetically, ambulant cases are, in fact, part of the FCMD spectrum.
人类9q GT多态性图谱的构建。
影响因子：
4.4
作者：
Kwiatkowski,DJ;Henske,EP;Weimer,K;Ozelius,L;Gusella,JF;Haines,J
通讯作者：
Haines,J
染色体 9q32-34 上 hexabrachion 基因 (HXB) 的二核苷酸重复多态性。
影响因子：
3.5
作者：
Ozelius,L;Schuback,DE;Stefansson,K;Slaugenhaupt,S;Gusella,JF;Breakefield,XO
通讯作者：
Breakefield,XO