A Japanese case of ichthyosis follicularis with atrichia and photophobia syndrome with an MBTPS2 mutation

Abstract

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 membranebound transcription factor protease, site 2 (MBTPS2) gene in European patients with this syndrome. In this study, we detected the 1286G4A (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.

Expanding the phenotype of IFAP/BRESECK syndrome: A new case with severe hypogammaglobulinemia

“…Recently a patient with the p.I258.M mutation was described with mild B cell lymphopenia and poor antibody response [6]. Other authors have reported atopic features like urticaria, atopic dermatitis, cow's milk protein allergy and anaphylaxis [3,4,11,16]. The presence of hypogammaglobulinemia in our patient might suggest a primary B lymphocyte disfunction in IFAP/BRESHECK syndrome playing a role in the pathogenesis of recurrent skin and respiratory tract infections.…”

“…The first reported patients were two male brothers of a German family with IFAP syndrome, who both died in the first 2 years after birth [3]. The third report was a 5 years-old Japanese male patient with IFAP syndrome [4]. The fourth report was a 4 years-old Japanese male patient with BRESHECK syndrome [7].…”

“…We describe a male patient with the p.Arg429His mutation in MBTPS2, which has been reported to be associated with the most severe phenotype in patients with IFAP [3,4] and BRESEK/BRE-SHECK syndrome [7].…”

Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome

“…Recurrent infections are often noted in IFAP syndrome. External genitalia are almost always normal; few cases presented with cryptorchidism [3,14,16,17], and one with a hypospadias [17]. Dental development is normal.…”

“…Nevertheless, no clear phenotype/genotype correlation could be evidenced. Indeed, recently a Japanese patient with IFAP syndrome carrying the c.1286G > A (p.Arg429His) mutation in MBTPS2, was not as severely affected as the patients from a German family carrying the same mutation [16,17]. Furthermore, it was shown that the p.Asn508Ser mutation causes IFAP syndrome and a close allelic syndrome named "Keratosis follicularis spinulosa decalvans" [17,27].…”