Lemmers Richard J F L, Wohlgemuth Mariëlle, Frants Rune R, Padberg George W, Morava Eva, van der Maarel Silvere M
Leiden University Medical Center, Center for Human and Clinical Genetics, Department of Human Genetics, Leiden, The Netherlands.
Am J Hum Genet. 2004 Dec;75(6):1124-30. doi: 10.1086/426035. Epub 2004 Oct 4.
Facioscapulohumeral muscular dystrophy (FSHD) is associated with contractions of the D4Z4 repeat in the subtelomere of chromosome 4q. Two allelic variants of chromosome 4q (4qA and 4qB) exist in the region distal to D4Z4. Although both variants are almost equally frequent in the population, FSHD is associated exclusively with the 4qA allele. We identified three families with FSHD in which each proband carries two FSHD-sized alleles and is heterozygous for the 4qA/4qB polymorphism. Segregation analysis demonstrated that FSHD-sized 4qB alleles are not associated with disease, since these were present in unaffected family members. Thus, in addition to a contraction of D4Z4, additional cis-acting elements on 4qA may be required for the development of FSHD. Alternatively, 4qB subtelomeres may contain elements that prevent FSHD pathogenesis.
面肩肱型肌营养不良症（FSHD）与4号染色体长臂亚端粒区域的D4Z4重复序列收缩有关。在D4Z4远端区域存在两种4号染色体长臂等位基因变体（4qA和4qB）。尽管这两种变体在人群中的出现频率几乎相同，但FSHD仅与4qA等位基因相关。我们鉴定出三个患有FSHD的家系，其中每个先证者都携带两个FSHD大小的等位基因，并且在4qA/4qB多态性上是杂合的。分离分析表明，FSHD大小的4qB等位基因与疾病无关，因为它们存在于未受影响的家庭成员中。因此，除了D4Z4收缩外，FSHD的发生可能还需要4qA上的其他顺式作用元件。或者，4qB亚端粒可能包含阻止FSHD发病机制的元件。
