A novel mutation in the XPA gene results in two truncated protein variants and leads to a severe XP/neurological symptoms phenotype.
BACKGROUND
The nucleotide excision repair (NER) pathway repairs UV-induced DNA lesions in an accurate fashion and prevents UV-irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found to be defective in xeroderma pigmentosum (XP) complementation group A patients.


OBJECTIVE
Characterization of four new XP-A patients.


METHODS
Genomic and cDNA sequencing, post-UV cell survival of living cells, host-cell reactivation of patients' fibroblasts and Western blotting.


RESULTS
One of the four investigated patients shows a novel mutation leading to two different truncated protein variants. Three patients contain the already described p.R228X mutation. All patient cell lines exhibit a strong UVC sensitivity and reduced NER capability. In most of the cases stable protein expression was detected.


CONCLUSIONS
We discovered four new XP-A patients and a novel XPA mutation resulting in two diverse patient alleles.
Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.
J
J
Lehmann
Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.
S
S
Schubert
Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.
A
A
Schäfer
Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.
P
P
Laspe
Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center Heidelberg, Heidelberg, Germany.
H A
HA
Haenssle
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center, Georg August University, Göttingen, Germany.
A
A
Ohlenbusch
Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Mannheim, Germany.|Institute of Carcinogenesis, NN Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia.|Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk, Russia.
A
A
Gratchev
Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.
S
S
Emmert
D000293:Adolescent; D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics*; D005347:Fibroblasts; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics; D008297:Male; D009154:Mutation; D010641:Phenotype; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D013064:Speech Disorders / Q000150:complications / Q000235:genetics; D014983:Xeroderma Pigmentosum / Q000150:complications / Q000235:genetics*; D051760:Xeroderma Pigmentosum Group A Protein / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult
D012333:RNA, Messenger; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein