SMCHD1 and Immunodeficiency: The second gene identified as FSHD2 disease gene is DNMT3B. Heterozygous mutations in DNMT3B have been linked to FSHD2, while biallelic mutations in DNMT3B cause the Immunodeficiency, Centromeric instability, Facial anomalies type I (ICF1) syndrome (OMIM #242860)42,43.