Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD
AuthorShepard, PJ; Barshop, BA; Baumgartner, MR; Jepsen, K; Hansen, John-Bjarne; Smith, EN; Frazer, Kelly
Methods: We performed exome sequencing on DNA from 33 cases and 108 healthy controls. We examined these data for associations between either MCC mutational status, genetic ancestry, or consanguinity and the absence or presence/specificity of clinical symptoms in MCCD cases.
Results: We determined that individuals with nonspecific clinical phenotypes are highly inbred compared with cases that are asymptomatic and healthy controls. For 5 of these 10 individuals, we discovered a homozygous damaging mutation in a disease gene that is likely to underlie their nonspecific clinical phenotypes previously attributed to MCCD.
Conclusion: Our study shows that nonspecific phenotypes attributed to MCCD are associated with consanguinity and are likely not due to mutations in the MCC enzyme but result from rare homozygous mutations in other disease genes.