title: Strict sun protection results in minimal skin changes in a patient with xeroderma pigmentosum and a novel c.2009delG mutation in XPD (ERCC2).
abstract: We examined the clinical, molecular and genetic features of a 16-year-old boy (XP2GO) with xeroderma pigmentosum (XP) and progressive neurological symptoms. The parents are not consanguineous. Increased sun sensitivity led to the diagnosis of XP at 2 years of age and a strict UV protection scheme was implemented. Besides recurrent conjunctivitis and bilateral pterygium, only mild freckling was present on his lips. He shows absent deep tendon reflexes, progressive sensorineural deafness and progressive mental retardation. MRI shows diffuse frontal cerebral atrophy and dilated ventricles. Symptoms of trichothiodystrophy (brittle hair with a tiger-tail banding pattern on polarized microscopy) or Cockayne syndrome (cachectic dwarfism, cataracts, pigmentary retinopathy and spasticity) were absent. XP2GO fibroblasts showed reduced post-UV cell survival (D(37) = 3.8 J/m(2)), reduced nucleotide excision repair, reduced expression of XPD mRNA and an undetectable level of XPD protein. Mutational analysis of the XPD gene in XP2GO revealed two different mutations: a common p.Arg683Trp amino acid change (c.2047C>T) known to be associated with XP and a novel frameshift mutation c.2009delG (p.Gly670Alafs*39). The latter mutation potentially behaves as a null allele. While not preventing neurological degeneration, early diagnosis and rigorous sun protection can result in minimal skin disease without cancer in XP patients.
authors.affiliation: Department of Dermatology, Georg-August-University Goettingen, Goettingen, Germany. semmert@gwdg.de
authors.forename: Steffen
authors.initials: S
authors.lastname: Emmert
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueda
authors.forename: Urs
authors.initials: U
authors.lastname: Zumsteg
authors.forename: Peter
authors.initials: P
authors.lastname: Weber
authors.forename: Sikandar G
authors.initials: SG
authors.lastname: Khan
authors.forename: Kyu-Seon
authors.initials: KS
authors.lastname: Oh
authors.forename: Jennifer
authors.initials: J
authors.lastname: Boyle
authors.forename: Petra
authors.initials: P
authors.lastname: Laspe
authors.forename: Karolin
authors.initials: K
authors.lastname: Zachmann
authors.forename: Lars
authors.initials: L
authors.lastname: Boeckmann
authors.forename: Christiane
authors.initials: C
authors.lastname: Kuschal
authors.forename: Andreas
authors.initials: A
authors.lastname: Bircher
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Kraemer
mesh_terms: D000293:Adolescent; D004252:DNA Mutational Analysis; D004260:DNA Repair; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D012867:Skin / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000517:prevention & control; D013472:Sunlight / Q000009:adverse effects*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000473:pathology*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human