Lo Bryan, Faiyaz-Ul-Haque M, Kennedy S, Aviv R, Tsui L-C, Teebi Ahmad S
Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Am J Med Genet A. 2003 Aug 15;121A(1):37-40. doi: 10.1002/ajmg.a.20226.
Cherubism is a rare autosomal dominant inherited condition caused by mutations in the c-Abl-binding protein SH3BP2. It is characterized by multiple cystic giant cell lesions of the jaw appearing in early childhood with stabilization and remission after puberty. In the present study, we used direct sequence analysis of the SH3BP2 gene of several individuals from a family with cherubism to search for additional SH3BP2 mutations resulting in cherubism. In affected relatives, we found a previously unreported G to A transition in exon 9 leading to a Gly to Arg substitution at amino acid position 420. G420R has been reported previously with a G to C transversion. To date there have been no disease causing mutations outside exon 9. Therefore, the amino acid sequence from positions 415 to 420 may represent a specific protein domain which, when disrupted, leads to the cherubism phenotype.
cherubism是一种罕见的常染色体显性遗传性疾病，由c-Abl结合蛋白SH3BP2的突变引起。其特征是在儿童早期出现颌骨多发性囊性巨细胞病变，青春期后病情稳定并缓解。在本研究中，我们对一个患有cherubism的家族中的几个个体进行了SH3BP2基因的直接序列分析，以寻找导致cherubism的其他SH3BP2突变。在受影响的亲属中，我们在第9外显子中发现了一个以前未报道的G到A的转换，导致第420位氨基酸由甘氨酸替换为精氨酸。G420R先前已有报道，是由G到C的颠换。迄今为止，在第9外显子之外尚未发现致病突变。因此，第415至420位的氨基酸序列可能代表一个特定的蛋白质结构域，当该结构域被破坏时，会导致cherubism表型。
