The genes encoding for D4Z4 binding proteins HMGB2, YY1, NCL, and MYOD1 are excluded as candidate genes for FSHD1B
The genes encoding for D4Z4 binding proteins HMGB2, YY1, NCL, and MYOD1 are excluded as candidate genes for FSHD1B
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DOI：
10.1016/j.nmd.2004.12.006
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发表时间：
2005-04-01
影响因子：
2.8
通讯作者：
Gilbert, JR
中科院分区：
文献类型：
--
作者：
Bastress, KL;Stajich, JM;Gilbert, JR
面肩肱骨肌营养不良症是一种骨骼肌疾病，其症状包括面部和肩带无力，并在大多数病例中进展到骨盆带和四肢。对于大多数FSHD病例，该疾病的分子基础可以确定为4号染色体长臂末端D4Z4重复序列的部分缺失。然而，在多达5%的FSHD家庭中，与4q35没有联系。这些案例被指定为FSHD1B。已经鉴定出与染色体4q35的D4Z4重复序列结合的蛋白质。我们研究了编码D4Z4结合蛋白YY1、HMGB2、NCL和MYOD1的基因作为FSHD1B的候选基因。对HMBG2的编码序列和启动子区域进行分析，未发现序列变异。对于YY1，分析了所有五个外显子，在未受影响和受影响的人群中都检测到多态性。在核仁蛋白（NCL）中，鉴定出几个SNP，包括导致非同义变化的SNP P515H；然而，所有的多态性要么发生在对照样本中，要么以前报道过。在MYOD1中也检测到一种新的多态性，但不代表疾病特异性变异。这些结果表明，HMBG2、YY1、NCL和MYOD1不太可能代表这些家族中负责FSHD的基因。(c) 2005 Elsevier B.V.版权所有
Facioscapulohumeral muscular dystrophy is a disease of skeletal muscle, with symptoms including both facial and shoulder girdle weakness and progression to involve the pelvic girdle and extremities in the majority of cases. For most cases of FSHD, the molecular basis of the disease can be identified as a partial deletion of the D4Z4 repeat array on the end of the long arm of chromosome 4. However, in up to 5% of FSHD families there is no linkage to 4q35. These cases are designated as FSHD1B. Proteins have been identified that bind to the D4Z4 repeats of chromosome 4q35. The genes encoding D4Z4 binding proteins YY1, HMGB2, NCL, and MYOD1 were investigated as candidate genes for FSHD1B. Coding sequences and promoter region were analyzed for HMBG2 and no sequence variations were detected. For YY1, all five exons were analyzed and a polymorphism was detected in both the unaffected and affected populations. In nucleolin (NCL), several SNPs were identified, including a SNP causing the non-synonymous change P515H; however, all polymorphisms either occurred in control samples or were previously reported. A novel polymorphism was also detected in MYOD1, but did not represent a disease-specific variation. These results suggest that HMBG2, YY1, NCL, and MYOD1 are unlikely to represent the genes responsible for FSHD in these families. (c) 2005 Elsevier B.V. All rights reserved.