Mutations causing Bloom syndrome have been identified in two new genes by an international collaboration of scientists including also researchers of the Institute of Human Genetics Göttingen. Bloom syndrome is a rare congenital disorder characterized by primary microcephaly, growth retardation, skin affections and intellectual disability. Patients with Bloom syndrome are also predisposed to the development of cancer, with a mean age of onset in the third decade of life.

The researchers in Göttingen investigated a Turkish family with two cousins who manifested developmental delay, mild intellectual disability, pronounced primary microcephaly and short stature and were clinically diagnosed with a Bloom syndrome-like disorder. Exome sequencing identified in both affected individuals a homozygous 5-bp deletion in RMI1 as the underlying cause of the condition. The protein encoded by RMI1 is a member of the BRT protein complex – just like TOP3A, in which their collaboration partners in this study detected novel causative variants in 10 other patients with Bloom syndrome. The BTR complex plays an essential role in homologous recombination, an important mechanism in the repair of DNA damage. Homozygous mutations in BLM, another BTR component, have previously been described as causing Bloom syndrome.

The results of the study have been published in the American Journal of Human Genetics.

Martin C-A, Sarlós K, Logan CV, Thakur RS, Parry DA, Bizard AH, Leitch A, Cleal L, Ali NS, Al-Owain MA, Allen W, Altmüller J, Aza-Carmona M, Barakat BAY, Barraza-García J, Begtrup A, Bogliolo M, Cho MT, Cruz-Rojo J, Dhahrabi HAM, Elcioglu NH, GOSgene, Gorman GS, Jobling R, Kesterton I, Kishita Y, Kohda M, Le Quesne Stabej P, Malallah AJ, Nürnberg P, Ohtake A, Okazaki Y, Pujol R, Ramirez MJ, Revah-Politi A, Shimura M, Stevens P, Taylor RW, Turner L, Williams H, Wilson C, Yigit G, Zahavich L, Alkuraya FS, Surralles J, Iglesais A, Murayama K, Wollnik B, Dattani M, Heath KE, Hickson ID, Jackson AP. Mutations in TOP3A Cause a Bloom Syndrome-like Disorder. Am J Hum Genet. 2018;103(2):221-231. doi:10.1016/j.ajhg.2018.07.001.