Whole-exome sequencing identifies mutations in MYMK in a mild form of Carey-Fineman-Ziter syndrome
Author(s): Hadil Alrohaif, Ana Töpf, Teresinha Evangelista, Monkol Lek, Daniel McArthur, Hanns Lochmüller
Published: March 19, 2018
Journal: Neurology Genetics
Fusion of single-nucleated myoblasts is essential for the formation of multinucleated myocytes. Mechanisms that regulate myoblast fusion have been a focus of recent studies.1,–,4 Transmembrane protein 8 (TMEM8C), also known as myomaker, is a highly conserved muscle-specific transmembrane protein encoded by the MYMK gene. The protein is expressed during early muscle development. Mymk-null mice die soon after birth because of skeletal muscle deficiency. In these mice, skeletal muscle tissue is present but consists of a smaller number of mononucleated cells indicating failure of myoblast cell fusion.1 Myomaker is also expressed during muscle regeneration when it coordinates fusion of satellite cells with residual muscle fibers to regenerate the damaged muscle tissue. In the absence of myomaker, adult mouse muscle tissue is unable to regenerate.5
In humans, mutations in the MYMK gene have recently been described in 8 individuals (aged 7–37 years) from 3 families with Carey-Fineman-Ziter syndrome (CFZS), a syndrome encompassing a congenital myopathy with marked facial weakness and Pierre Robin sequence, among other consistent features.6
Here, we report an additional and the oldest known patient-bearing mutations in the MYMK gene, identified through whole-exome sequencing (WES). We provide insights into disease progression, as well as ascertain features associated with the disorder.