Submission Details

Autosomal recessive

06/04/2019

The MYMK gene, previously referred to as TMEM8C, is located on chromosome 9 at 9q34.2 and encodes the transmembrane Myomaker protein, which is required for myoblast fusion and the formation of multinucleated myofibers during skeletal muscle development and regeneration. The MYMK gene was first reported in relation to autosomal recessive Carey-Fineman-Ziter syndrome in 2017 (28681861: Di Gioia et al. 2017). At least six unique variants, all missense, have been reported in humans. A majority of individuals carry one copy of the p.Pro91Thr variant. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in seven unrelated probands in three publications (28681861: Di Gioia et al. 2017; 29560417: Alrohaif et al. 2018; 30065953: Hedberg-Oldfors et al. 2018). Variants in this gene segregated with disease in five additional family members, but none of the families met criteria for scoring segregation. Homozygous loss of function is implicated as the mechanism of disease. This gene-disease relationship is also supported by expression data, in vitro functional analyses of reported variants, mouse and zebrafish models, and rescue in the zebrafish model (23868259: Millay et al. 2013; 28681861: Di Gioia et al. 2017). In summary, there is strong evidence to support the relationship between MYMK and Carey-Fineman-Ziter syndrome, autosomal recessive. An additional report in humans published three years from the first proposal of the association is needed to reach a definitive classification.

23868259 28681861 29560417 30065953