14 March 2018
Embryonic development disorders linked to two genes
Published online 27 January 2011
Carnevale, Mingarelli, Malpuech and Michels are three rare development disorders that have dramatic effects on foetal development, including facial dysmorphism, cleft lip and palate, learning disabilities and limb abnormalities.
A group of researchers, including two researchers from the King Faisal Specialist Hospital and King Saud University in Saudi Arabia, have investigated the etiology of these overlapping symptoms to prove whether they are in fact one syndrome as suspected, a condition dubbed 3MC.
They studied 11 families diagnosed with one of the four syndromes and identified two mutated genes COLEC11 and MASP1 present in all confirming that these disorders are indeed a single condition and published their results today in Nature Genetics.
These genes encode the proteins CL-K1, MASP-1/MASP-3, which are involved in immunity and are highly expressed in tissues of embryonic mice. They next studied the role of CL-K1 in the disease and found that it must act independently of the downstream complement cascade activation in 3MC.
The absence of the CL-K1 and MASP-3 proteins during zebrafish development, a model to study action of the proteins, led to multisystem abnormalities, including craniofacial defects and skeletal, renal and neuronal problems. Since CL-K1 and MASP-3 are activated through the lectin pathway, the authors suggest focusing on its role in embyrogensis and in craniofacial development.
- Rooryck, C et al. Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nature Genetics. 23 January 2011. doi: 10.1038/ng.757