Novel mutations in the MRE11 gene cause Seckel syndrome

Abstract

Seckel syndrome is an autosomal recessive disorder characterized by severe microcephaly, growth retardation and bird-like face. Recently, it was reported that mutations of ATR or PCNT gene caused Seckel syndrome. However, it is considered that other genes are also responsible for Seckel syndrome. Here, we report that novel mutations in MRE11 gene cause Seckel syndrome. We identified MRE11 mutations in 2 Japanese patients. Patient1 had biallelic splice site mutations, and Patient2 had splice site mutation and missense mutation in the MRE11 gene. The expression levels of Mre11, Nbs1 and Rad50 proteins were reduced in both the patients. Also, cells from the patients showed chromosomal instability and X-ray hypersensitivity. Next, we examined the intercellular distribution of Mre11 protein. Immunostaining indicated that Mre11 protein was co-localized with the centrosomal protein gamma-tubulin. Furthermore, the patient's cells showed abnormal centrosome amplification. It is under study about functional roles of Mre11 protein in centrosome.