Recently, Wojciech Wisniewski and company found a deletion that eliminates an exon of the gene TM4SF20, a transmembrane protein expressed in the brain. The mutant protein is terminated prematurely and apparently accumulates inside the cell.
This mutation causes severe language delay, and also causes ominous-looking MRI brain scans, with white matter hypertensities (WMHs) scattered over the brain. Normally those spots are the result of brain aging, something you see in octogenarians. Incredibly rare in kids.
So far this is mildly interesting, in a depressing sort of way, but the genetics journals are full of new ways for your genes to screw you. Almost always, those newly discovered genetic syndromes are extremely rare, sometimes limited to a a single family. Mutation creates them, selection cuts them down.
But this one is common, at least in Southeast Asia. It’s a dominant – one copy causes trouble – and the gene frequency looks to be around 1% in Vietnam. It’s also been seen in people from Burma, Thailand, Indonesia, and the Philippines, although there’s no estimate of the frequency in those countries yet.
This is weird. Deleterious dominants should never be common, certainly not in a big population. It’s rather like those claims about a common dominant form of prosopagnosia – but the guy making that claim was probably just wrong. This one sounds real – they have found the gene, they seem to have good evidence of severe language delay in carriers, careful MRI studies, have done mouse genetic studies, etc. And the carrier parents report language delays in their own childhoods.
The kids seem to eventually catch up in language, at least to some extent. Some of the parents are smart, or at any rate have had academic success. Still, it’s hard to believe that all those funny-looking spots on the MRI brain scans are harmless – particularly with increasing age.
It’s a puzzle. Probably not to the authors, who come out of the medical world, but it is to me.