Recurrent MBTPS2 variant c.970+5G>A in IFAP syndrome: a mutational hotspot

Abstract Ichthyosis follicularis, alopecia and photophobia (IFAP) syndrome type I is a rare, X-linked disorder resulting from pathogenic variants in MBTPS2 . Here we report a Pakistani IFAP pedigree of three affected individuals harboring the recurrent MBTPS2 splice-site variant c.970+5G>A that was reported previously in Chinese and Argentinian families. Haplotype analyses across these three families excluded a founder effect, establishing c.970+5G>A as a recurrent mutational hotspot. In addition, phenotypic severity varied across the families, suggesting additional modifiers.