While pHLH results from homozygous mutations in predominantly autosomal recessive genes (e.g., STX11), certain heterozygous hypomorphic or missense dominant-negative mutations in these same genes (e.g., PRF1 [21,22], STXBP2 [23,24], UNC13D [25] RAB27A) [11] have been reported to contribute to CSS, [26] often in combination with an inciting viral infection, via a threshold model of disease [27]. Here, PRF1 is linked to viral infectious disease.