Increased TBX6 Gene Dosages Induce Congenital Cervical Vertebral Malformations in Humans and Mice

We previously reported that the human 16p11.2 BP4-BP5 deletion and its associated TBX6 dosage reduction caused congenital vertebral malformations (CVMs) in thoracic and lumber vertebrae. Here we reveal genetic contributions of the reciprocal 16p11.2 BP4-BP5 duplication to cervical CVMs. The spinal assessments in seven duplication carriers showed that four presented characteristics of cervical CVMs. We also generated the mouse model that functionally mimics the TBX6 dosage of duplication carriers. Remarkably, 60% of the mutated mice manifested with cervical CVMs. Our findings in humans and mice consistently support that an increased TBX6 dosage contributes to the risk of developing cervical CVMs. (By Professor Feng Zhang, https://jmg.bmj.com/content/early/2019/12/30/jmedgenet-2019-106333 )

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