Ichthyosis follicularis with atrichia and photophobia (IFAP) syndrome is a rare genetic disorder characterized by the triad of ichthyosis follicularis, alopecia and photophobia. Previous studies have identified five missense mutations in the membrane-bound transcription factor protease, site 2 (MBTPS2) gene in European patients with this syndrome. In this study, we detected the 1286G>A (Arg429His) mutation in MBTPS2 in a Japanese patient with IFAP syndrome. This mutation has previously been detected in a German family with this syndrome. Functional analysis revealed that this mutation was the most severe mutation identified to date for this syndrome. None of the male German patients had been tested for the mutation because they had several visceral and bone anomalies, and had died as neonates or infants. The clinical features of our 5-year-old patient are less severe than those of the German patients. Although he has neurological abnormalities, such as retarded psychomotor development and seizures, he does not have bone or visceral anomalies, except cryptorchidism. This case indicates the existence of other factor(s) that influence the clinical features of this syndrome. Further clinical and genetic studies are required to clarify the relationship between phenotypes and genotypes and to identify such modifying factors.
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