Through whole exome sequencing, the new study found a single gene at the root of seemingly distinct types of MCD in children from multiple families. Rather than scanning a person's entire genome for mutations, this technique focuses on the protein-coding bits of DNA, or exome, which makes up about 1.5 percent of the genome.
Genetic forms of MCD occur worldwide and in all kinds of families, but the highest incidence is among children born to parents who are related. Dr. Gunel and his colleagues at Yale teamed up with investigators in Turkey to study Turkish families with MCD. The country has a tradition of first- and second-cousin marriages, and thus a relatively high incidence of MCD.
The study began by focusing on two related children who were diagnosed with microcephaly. Whole exome sequencing revealed that both children had mutations in a gene called WDR62. As the study grew to include children from other families with microcephaly, many of the children were found to have mutations in the same gene. Unexpectedly, brain imaging revealed that the children also tended to have other types of MCD, superimposed with microcephaly. In all, the investigators found 6 unique mutations in the WDR62 gene among 30 families.
Those results show that a single gene "is required for strikingly diverse aspects of human cortical brain development," said Dr. Gunel.
No one knows precisely what WDR62 does, but related proteins are known to regulate the processing of RNA (the intermediate between
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NIH/National Institute of Neurological Disorders and Stroke