Basson C T, Bachinsky D R, Lin R C, Levi T, Elkins J A, Soults J, Grayzel D, Kroumpouzou E, Traill T A, Leblanc-Straceski J, Renault B, Kucherlapati R, Seidman J G, Seidman C E
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Nat Genet. 1997 Jan;15(1):30-5. doi: 10.1038/ng0197-30.
Holt-Oram syndrome is characterized by upper limb malformations and cardiac septation defects. Here, we demonstrate that mutations in the human TBX5 gene underlie this disorder. TBX5 was cloned from the disease locus on human chromosome 12q24.1 and identified as a member of the T-box transcription factor family. A nonsense mutation in TBX5 causes Holt-Oram syndrome in affected members of one family; a TBX5 missense mutation was identified in affected members of another. We conclude that TBX5 is critical for limb and heart development and suggest that haploinsufficiency of TBX5 causes Holt-Oram syndrome.
Holt-Oram综合征的特征是上肢畸形和心脏间隔缺损。在此，我们证明人类TBX5基因突变是这种疾病的病因。TBX5是从人类12号染色体q24.1区域的疾病位点克隆出来的，并被鉴定为T-box转录因子家族的成员。TBX5基因中的一个无义突变导致一个家族中的患病成员出现Holt-Oram综合征；在另一个家族的患病成员中鉴定出一个TBX5错义突变。我们得出结论，TBX5对肢体和心脏发育至关重要，并表明TBX5的单倍体不足导致了Holt-Oram综合征。
