Neurological symptoms and natural course of xeroderma pigmentosum.
We have prospectively followed 16 Finnish xeroderma pigmentosum (XP) patients for up to 23 years. Seven patients were assigned by complementation analysis to the group XP-A, two patients to the XP-C group and one patient to the XP-G group. Six of the seven XP-A patients had the identical mutation (Arg228Ter) and the seventh patient had a different mutation (G283A). Further patients were assigned to complementation groups on the basis of their consanguinity to an XP patient with a known complementation group. The first sign of the disease in all the cases was severe sunburn with minimal sun exposure in early infancy. However, at the time the diagnosis was made in only two cases. The XP-A patients developed neurological and cognitive dysfunction in childhood. The neurological disease advanced in an orderly fashion through its successive stages, finally affecting the whole nervous system and leading to death before the age of 40 years. Dermatological and ocular damage of the XP-A patients tended to be limited. The two XP-C patients were neurologically and cognitively intact despite mild brain atrophy as seen by neuroimaging. The XP-G patients had sensorineural hearing loss, laryngeal dystonia and peripheral neuropathy. The XP-C patients had severe skin and ocular malignancies that first presented at pre-school age. They also showed immunosuppression in cell-mediated immunity. Neurological disease appears to be associated with the complementation group and the failure of fibroblasts to recover RNA synthesis following UV irradiation, but not necessarily to the severity of the dermatological symptoms, the hypersensitivity of fibroblasts to UVB killing or the susceptibility of keratinocytes to UVB-induced apoptosis.
Anttinen
Anu
A
Department of Neurology, Turku University Central Hospital, PB 52, 20521 Turku, Finland. anu.anttinen@tyks.fi
Koulu
Leena
L
Nikoskelainen
Eeva
E
Portin
Raija
R
Kurki
Timo
T
Erkinjuntti
Matti
M
Jaspers
Nicolaas G J
NG
Raams
Anja
A
Green
Michael H L
MH
Lehmann
Alan R
AR
Wing
Jonathan F
JF
Arlett
Colin F
CF
Marttila
Reijo J
RJ
D000328:Adult; D001927:Brain Diseases / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005128:Eye Diseases / Q000209:etiology; D005260:Female; D005387:Finland; D005816:Genetic Complementation Test; D006311:Hearing Disorders / Q000209:etiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009483:Neuropsychological Tests; D009687:Nuclear Proteins / Q000235:genetics; D011446:Prospective Studies; D012871:Skin Diseases / Q000209:etiology; D014057:Tomography, X-Ray Computed; D014157:Transcription Factors / Q000235:genetics; D014983:Xeroderma Pigmentosum / Q000150:complications / Q000523:psychology*; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics; D000099250:DNA Excision Repair Protein ERCC-5
D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D051760:Xeroderma Pigmentosum Group A Protein; D000099250:DNA Excision Repair Protein ERCC-5; C497314:XPA protein, human; C086984:XPC protein, human