SMC3 Mutation - Cornelia de Lange Syndrome

Nearly always, Cornelia de Lange Syndrome happens when a new gene mutation occurs in a child. Most commonly there is a mutation in the NIPBL gene, which was first linked to CdLS in 2004. Since then, mutations in a handful of other genes—SMC3 is one of them—have been found to cause syndromes overlapping with CdLS, but these mutations are much less well understood. Nowadays, researchers have the ability to produce animal models for almost any genetic disease. Mice, fish and flies with NIPBL mutations are studied in labs around the world, and helped the scientific community work out how that type of CdLS arises. No such models are studied for SMC3, however, so even basic facts about it remain unknown. This makes it difficult to predict how SMC3-CdLS might respond to different kinds of therapies. My goal is to raise funds to jump-start such research, creating one or more animal models of SMC3-CdLS and exploiting them to find new treatments.

SMC3 Mutation - Cornelia de Lange Syndrome

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Vihaan’s specific mutation is A485del (SMC3 – c.1453_1455del nucleotide, p.A485del). This is a spontaneous mutation which leads to defective cohesin complex expression. This falls under the broader disease types called cohesinopathies and transcriptomopathies. Here’s a great write up by my friend Peter Llyod-Thomas on CdLS.

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Birth Weight, Growth and Head Size

Developmental Delays

Gastrointestinal Involvement

Behavioral Issues

Facial Features

Limb Differences

Other System Abnormalities

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Currently there are no FDA approved treatments.

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to Vihaan and other kids

affected by CdLS