ABCC6 mutations in pseudoxanthoma elasticum: an update including eight novel ones.
OBJECTIVE
Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder of connective tissue, affecting the retina, the skin, and the cardiovascular system. PXE is caused by mutations in ABCC6. Up to now, the literature reports that there are 180 different ABCC6 mutations in PXE. The purpose of this paper is to report eight novel mutations in ABCC6 and to update the spectrum and frequency of ABCC6 mutations in PXE patients.


METHODS
Eye, skin, and DNA examinations were performed using standard methodologies. We newly investigated the gene in 90 probands by denaturing high-performance liquid chromatography (dHPLC) and direct sequencing. We examined a total of 166 probands.


RESULTS
Eight novel ABCC6 mutations (c.1685T>C, p.Met562Thr; c.2477T>C, p.Leu826Pro; c.2891G>C, p.Arg964Pro; c.3207C>A, p.Tyr1069X; c.3364delT, p.Ser1122fs; c.3717T>G, p.Tyr1293X; c.3871G>A, p.Ala1291Thr; c.4306_4312del, p.Thr1436fs) were found in seven unrelated patients. Currently, our mutation detection score is at least one ABCC6 mutation in 87% of patients with a clinical diagnosis of PXE.


CONCLUSIONS
Our results support that ABCC6 is the most important, and probably the only, causative gene of PXE. In total, 188 different ABCC6 mutations have now been reported in PXE in the literature.
Plomp
Astrid S
AS
Department of Clinical and Molecular Ophthalmogenetics, Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
Florijn
Ralph J
RJ
Ten Brink
Jacoline
J
Castle
Bruce
B
Kingston
Helen
H
Martín-Santiago
Ana
A
Gorgels
Theo G M F
TG
de Jong
Paulus T V M
PT
Bergen
Arthur A B
AA
D000595:Amino Acid Sequence; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D017124:Conserved Sequence; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D011561:Pseudoxanthoma Elasticum / Q000235:genetics* / Q000473:pathology; D012160:Retina / Q000473:pathology; D012867:Skin / Q000473:pathology
D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human