Re: Can mutations in the non-coding region of a gene result in disease?

The answer to your general question is yes, mutations in non-coding regions of a gene can result in disease. Such mutations could lead to changes in gene expression or splicing, which in turn have the potential to alter gene function.

Comparatively little is known about such mutations for practical reasons: the non-coding region of a gene is much larger and harder to identify than the coding region. For instance, regions that regulate expression of a gene hundreds of kilobases away from the coding region have been described recently (see http://simurl.com/rapsoh ). This greatly complicates defining the sizes of genes and therefore the area that needs to be examined for mutations.

Even considering just the intronic regions multiplies the amount of sequencing needed to look for potential disease-causing mutations. This work is underway, and is focusing on genes strongly correlated with heritable disease, such as BRCA1 and 2 (for one example, see http://simurl.com/wefsid ). I have a colleague here who is doing this type of analysis for heritable difficiencies in anti-oxidant activity where coding-region mutations cannot account for the difficiencies.

For the particular case of CYP1B1, the size of the transcribed gene is relatively small, with only two introns, so it should be relatively easy to look for mutations in those non-coding regions. Like you, I could not find an investigation of the non-coding regions of CYP1B1.

[Moderator's Note: As reported by Kazazian and Boehm in 1988, most of the mutations that cause beta-thalassemia are in the non-coding regions of the beta-globin gene. Since then many genetic disorders have been linked to defective RNA splicing and stability.]