No apparent neurologic defect in a patient with xeroderma pigmentosum complementation group D

Ichihashi, Masamitsu

doi:10.1001/archderm.124.2.256

Cited by 7 publications

(5 citation statements)

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“…A possible interpretation of the data could be that the extremely high UV-induced death rate in the embryos with the XP/CS mutations is mainly caused by UV-induced strand displacement in XP/CS cells ( Godon et al, 2012 ), whereas the modestly elevated rates seen in most XP and TTD mutants might reflect reduced NER. Interestingly, in cases where the human fibroblast lines allow an assessment of survival for a specific allele (R683W, R112H, R722W and possibly R601L, see below), similar UV sensitivities have been reported for XP and TTD mutants to those we see here (5×–12× elevated; Lehmann et al, 1988 ; Ichihashi et al, 1988 ; Broughton et al, 1994 ; Takayama et al, 1995 ; Takayama et al, 1996 ). The fibroblast line with the R601L allele carries, as the second allele, the D234N mutation.…”

Section: Resultssupporting

confidence: 83%

“…Compared with other TTD patients, patients with the R658C mutation show only mild neurological and developmental defects ( Bergmann and Egly, 2001 ), and R658C flies showed far fewer asynchronous waves than the other TTD alleles. Among the XP-type patients, those with an R683W mutation show the most severe neurological abnormalities ( Ichihashi et al, 1988 ; Taylor et al, 1997 ) and, in flies, R683W also gave the highest frequency of asynchronous waves, together with R601L.…”

Section: Discussionmentioning

confidence: 99%

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ADrosophilaXPD model links cell cycle coordination with neuro-development and suggests links to cancer

Stettler

Sandrock

et al. 2014

Disease Models &Amp; Mechanisms

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XPD functions in transcription, DNA repair and in cell cycle control. Mutations in human XPD (also known as ERCC2) mainly cause three clinical phenotypes: xeroderma pigmentosum (XP), Cockayne syndrome (XP/CS) and trichothiodystrophy (TTD), and only XP patients have a high predisposition to developing cancer. Hence, we developed a fly model to obtain novel insights into the defects caused by individual hypomorphic alleles identified in human XP-D patients. This model revealed that the mutations that displayed the greatest in vivo UV sensitivity in Drosophila did not correlate with those that led to tumor formation in humans. Immunoprecipitations followed by targeted quantitative MS/MS analysis showed how different xpd mutations affected the formation or stability of different transcription factor IIH (TFIIH) subcomplexes. The XP mutants most clearly linked to high cancer risk, Xpd R683W and R601L, showed a reduced interaction with the core TFIIH and also an abnormal interaction with the Cdk-activating kinase (CAK) complex. Interestingly, these two XP alleles additionally displayed high levels of chromatin loss and free centrosomes during the rapid nuclear division phase of the Drosophila embryo. Finally, the xpd mutations showing defects in the coordination of cell cycle timing during the Drosophila embryonic divisions correlated with those human mutations that cause the neurodevelopmental abnormalities and developmental growth defects observed in XP/CS and TTD patients.

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Section: Resultssupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

ADrosophilaXPD model links cell cycle coordination with neuro-development and suggests links to cancer

Stettler

Sandrock

et al. 2014

Disease Models &Amp; Mechanisms

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“…Arg601Leu mutation was previously reported in one Japanese woman, XP43KO. 11,12 She had heterozygous mutation of Arg601Leu and Asp234Asn. The patient was 31 years old and showed no apparent neurological abnormalities and rather mild or moderate skin lesions at that age.…”

Section: Discussionmentioning

confidence: 99%

Whole‐exome sequencing and host cell reactivation assay lead to a diagnosis of xeroderma pigmentosum group D with mild ultraviolet radiation sensitivity

et al. 2020

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A case of xeroderma pigmentosum (XP) group D in a 39-year-old Japanese man is reported. The patient had suffered from moderate to severe solar sensitivity and freckle-like pigmented macules in sun-exposed areas since 6 years of age, and developed skin malignancies such as squamous cell carcinoma, actinic keratosis, Bowen's disease and basal cell carcinoma. The minimal erythema dose for ultraviolet (UV) radiation was decreased with a delayed peak reaction. The level of unscheduled DNA synthesis of fibroblasts from the patient was 70% of normal, while they expressed POLH, a gene product responsible for the XP variant. Whole-exome sequencing indicated that the patient harbored a homozygous mutation of c.1802G>T, p.Arg601Leu in ERCC2. A genetic complementation test was carried out by host cell reactivation assay, which showed that the patient's fibroblasts recovered only when they were transfected with XPD cDNA, confirming the diagnosis of XP-D. Arg601Leu mutation in ERCC2 may be related to mild UV radiation sensitivity and moderate skin lesions.

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“…Most of the group D patients in the West manifest severe dermatological, ophthalmological and neurological symptoms that are almost equiva lent to those observed in the majority of group A patients [ 1,8,9]. Table 1 shows the characteristics of the 8 Japa nese group D cases [10][11][12][13][14][15]. All of them manifest mild or moderate cutaneous symptoms compared with those in group A [1,10].…”

Section: Discussionmentioning

confidence: 99%

Xeroderma pigmentosum Group D Patient Bearing Lentigo maligna without Neurological Symptoms

et al. 1990

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A 35-year-old Japanese female patient with xeroderma pigmentosum (XP), registered as XP114TO, was assigned to complementation group D by the cell fusion complementation test. The patient had manifested moderate solar sensitivity and freckles by the age of 6 years. The skin phototest using 290- and 300-nm monochromatic ultraviolet (UV) light revealed slightly lowered minimal erythema doses at 24 h after irradiation. The XP114TO skin fibroblasts exhibited about the 6-fold higher sensitivity to the lethal effect of 254-nm UV as did normal cells. Unscheduled DNA synthesis (UDS) induced in XP114TO cells by 254-nm UV (10 J/m²) was 33% of normal, falling into the group D range of 25–50% UDS. The patient developed lentigo maligna on the right side of the nose. Unlike the typical XP group D cases in the West, she showed no neurological abnormalities.

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No apparent neurologic defect in a patient with xeroderma pigmentosum complementation group D

Cited by 7 publications

References 0 publications

ADrosophilaXPD model links cell cycle coordination with neuro-development and suggests links to cancer

ADrosophilaXPD model links cell cycle coordination with neuro-development and suggests links to cancer

Whole‐exome sequencing and host cell reactivation assay lead to a diagnosis of xeroderma pigmentosum group D with mild ultraviolet radiation sensitivity

Xeroderma pigmentosum Group D Patient Bearing Lentigo maligna without Neurological Symptoms

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