In one case study a patient with homozygous pathogenic TMEM65 gene mutations suffered from severe mitochondrial encephalomyopathy (including microcephaly, mutism and global developmental delay) with seizures and developmental regression at age 3 years.100 In a GWAS study TMEM65 variants were associated with “fear of pain”101 and were differentially methylated in chronic widespread pain syndrome102 making it an interesting candidate for future studies. The gene discussed is TMEM65; the disease is Global developmental delay.