NAA10 polyadenylation signal variants cause syndromic microphthalmia

Polyadenylation signals direct the cleavage and polyadenylation of messenger RNA (mRNA). While it is known that polyadenylation is an important process for mRNA stability and function few polyadenylation signal variants have been identified as causative for human disease. Here we identify three distinct, novel variants in the polyadenylation signal of the NAA10 gene in three families with X-linked syndromic microphthalmia/anophthalmia. Functional studies suggest polyadenylation variants in NAA10 lead to partial loss of function due to reduced mRNA levels and we hypothesize that yet to be identified polyadenylation variants play a role in other human diseases that result from partial loss of function. Development of tools to detect, interrogate, and interpret polyadenylation signals will allow this work to yield benefits for the diagnosis of patients with other genetic disorders and contribute to the overall improvement in clinical genomic sequencing diagnostic yield. (By Dr Jennifer J Johnston, https://jmg.bmj.com/content/early/2019/03/06/jmedgenet-2018-105836)

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