FATP4 missense and nonsense mutations cause similar features in Ichthyosis Prematurity Syndrome

Maria Sobol,Niklas Dahl,Joakim Klar

doi:10.1186/1756-0500-4-90

Abstract

BackgroundIchthyosis Prematurity Syndrome (IPS) is an autosomal recessive disorder characterized by premature birth, non-scaly ichthyosis and atopic manifestations. The disease was recently shown to be caused by mutations in the gene encoding the fatty acid transport protein 4 (FATP4) and a specific reduction in the incorporation of very long chain fatty acids (VLCFA) into cellular lipids.FindingsWe screened probands from five families segregating IPS for mutations in the FATP4 gene. Four probands were compound heterozygous for four different mutations of which three are novel. Four patients were heterozygous and one patient homozygous for the previously reported non-sense mutation p.C168X (c.504c > a). All patients had clinical characteristics of IPS and a similar clinical course.ConclusionsMissense mutations and non-sense mutations in FATP4 are associated with similar clinical features suggesting that missense mutations have a severe impact on FATP4 function. The results broaden the mutational spectrum in FATP4 associated with IPS for molecular diagnosis of and further functional analysis of FATP4.

Highlights

Ichthyosis prematurity syndrome (IPS) is a rare form of autosomal recessive ichthyosis characterized by polyhydramnion and premature birth of the affected child [1,2,3]
Missense mutations and non-sense mutations in fatty acid transport protein 4 (FATP4) are associated with similar clinical features suggesting that missense mutations have a severe impact on FATP4 function
The results broaden the mutational spectrum in FATP4 associated with Ichthyosis Prematurity Syndrome (IPS) for molecular diagnosis of and further functional analysis of FATP4

Summary

Introduction

Ichthyosis prematurity syndrome (IPS) is a rare form of autosomal recessive ichthyosis characterized by polyhydramnion and premature birth of the affected child [1,2,3]. Newborns exhibit respiratory complications and a thick caseous desquamating epidermis. Patients suffer from a lifelong non-scaly ichthyosis with atopic manifestations. Ultrastructural analyses reveal membrane aggregations in the upper epidermal layers, and histological analysis of the skin reveal thickening of the epidermis. IPS is more prevalent in Norway and Sweden with an estimated local carrier frequency of one in 50 suggesting a founder mutation [1]. Ichthyosis Prematurity Syndrome (IPS) is an autosomal recessive disorder characterized by premature birth, non-scaly ichthyosis and atopic manifestations. The disease was recently shown to be caused by mutations in the gene encoding the fatty acid transport protein 4 (FATP4) and a specific reduction in the incorporation of very long chain fatty acids (VLCFA) into cellular lipids

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