FATP4 missense and nonsense mutations cause similar features in Ichthyosis Prematurity Syndrome - PubMed (original) (raw)

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

Maria Sobol et al. BMC Res Notes. 2011.

Abstract

Background: 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.

Findings: We 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.

Conclusions: Missense 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.

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Figures

Figure 1

Figure 1

Family pedigrees, mutation traces and positions of predicted amino acid substitutions in FATP4. Multiple sequence alignment is shown of FATP4 protein with orthologs from different species and with the FATP family of proteins. (a) Pedigrees of three of the five families from which healthy family members were available showing the segregation of mutations and IPS (b) Sequence chromatograms of the five mutations identified (c) Schematic overview of FATP4 functional domains; the N-terminal transmembrane region (TM), the ER localization signal (ERx; aa 47-102), the ATP/AMP motif involved in ATP binding and adenylate formation (ATP/AMP; aa 243-345) and the conserved FATP motif of importance for fatty acid binding (FATP; aa 500-551). The arrows indicate positions of the mutated amino acid residues reported herein associated with IPS (d) Multiple sequence alignment of selected regions of the human FATP4 protein and Fatp4 proteins from mouse and dog. Arrows indicate the position of the missense mutations at conserved residues (e) Multiple sequence alignment of FATP4 protein with the human FATP family of proteins (FATP1, FATP2, FATP3, FATP5, and FATP6). The positions of the missense mutations are indicated by arrows

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