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Table 1 Clinical and autopsy abnormalities in XP-A (XP12BE) and XP-D (XP18BE) patients compared to two XP-C patients

From: The influence of DNA repair on neurological degeneration, cachexia, skin cancer and internal neoplasms: autopsy report of four xeroderma pigmentosum patients (XP-A, XP-C and XP-D)

  Case 1 Case 2 Case 3 Case 4
  XP-A (XP12BE) (GM05509)* XP-D (XP18BE) (CRL1275)**(XPKABE) XP-C (XP24BE) (GM11638)* XP-C (XP1BE) (GM10881)*
  late onset juvenile form XP XP with neurological degeneration no neurological disease subclinical neurodegeneration
Age at death/Gender/DOB d44 yr/F b1965 d45 yr/F b1964 d35 yr/F b1972 d49 yr/F b1944
XP complementation group XP-A XP-D XP-C XP-C
Mutations (see text for details) compound heterozygote compound heterozygote compound heterozygote homozygous
CLINICAL FINDINGS     
Height 145.5 cm (<3 %ile) 165 cm (50–75 %ile) 153.3 cm - 34 yr (10 %ile) 160 cm (25–50 %ile)
Weight 32 kg (<3 %ile) 60.6 kg (50 %ile) 56.7 kg - 35 yr (50 %ile) 76.6 kg (50–75 %ile)
Cachexia? yes no no no
Acute skin sunburning on minimal exposure? yes yes no no
Freckle-like skin lesions on sun exposed skin? yes yes yes yes
Skin cancer?1 >200 BCC and 1 SCC 7 SCC and 2 BCC >200 (190-BCC,3 SCC and ~50 MIS) >200 (>35 BCC, >37 SCC, 2 soft tissue sarcoma, 28 MIS and 6 Mel)
Microcephaly? yes (2%ile) no no no
Hearing progressive high frequency sensorineural hearing loss progressive high frequency sensorineural hearing loss normal subclinical high frequency sensorineural hearing loss at 48 yr
Deep tendon reflexes absent absent (1995) normal normal at 37 yr, ankle hyporeflexia at 43 yr
Able to walk? no no yes yes
Able to talk? no no yes yes
Able to care for self? no no yes yes
Difficulty swallowing? yes - G-tube - age 37 yr yes - G-tube - age 44 yr normal normal
Primary ovarian failure? no unknown yes yes
Anterior eye abnormalities bilateral pinguecula, exposure keratopathy2 bilateral pinguecula, exposure keratopathy2 corneal scar, pterygium blateral orbital exenterations for infiltrative SCC of globe3
Eye - retinal degeneration optic nerve atrophy2 no2 no unknown
Imaging of brain diffuse cerebral and cerebellar atrophy (41 yr −2006) minimal cortical atrophy (19 yr- 1983) left frontal lobe tumor slight cerebral cortical atrophy and ventricular enlargement (44 yr)
AUTOPSY FINDINGS     
Thick calvarium? no yes; cortical sclerosis, no tumor seen no no
Brain weight [normal 1240 g (1050–1550)] 660g (~ 6mo) 760g (~1 yr) 1330g [normal] 1300g [normal]
Brain atrophy? yes - diffuse yes - diffuse no atrophy - tumor no, except optic nerves secondary to orbital exenteration
Dilated brain ventricles? yes yes asymmetric due to tumor no
Thin corpus callusum? yes yes no remarkable features no
Histological neuronal loss? yes - hippocampus, pons, medulla, midbrain, thinned cortex, small cerebellum yes – outer cortex (neuronal loss and vacuolization resembling status spongiosis), hippocampus (CA2 and CA3 regions), basal ganglia, cerebellum no remarkable features no
Histological gliosis? yes - midbrain, pons, medulla, basal ganglia, thalamus, hippocampus yes - cortex, hippocampus no remarkable features yes - molecular layer of cerebellum
Histological myelin pallor? yes - temporal lobe, frontal lobe, cerebellum yes - basal ganglia, cerebellum no remarkable features no remarkable features
Cerebellum Atrophy, loss of Purkinje cells with axonal swelling, Bergmann astrocytosis atrophy, patchy Purkinje cell loss no remarkable features moderate to marked Purkinje cell loss with Bergmann astrocyte proliferation
Dorsal root ganglia no remarkable features no remarkable features no remarkable features severe neuronal loss
Histology of peripheral nerves minimal focal perivascular inflammation in the adjacent connective tissue no pathologic changes femoral nerve - unremarkable median nerve mild focal interstital fibrosis, sural nerve - no pathologic diagnosis
EM of peripheral nerves axonal neuropathy not done not done not done
Eye pathology? neovascularization of cornea, optic atrophy2 neovascularization of cornea, cataract2 not done sockets of orbits lined with skin
Histology of muscles myofiber type -grouping no pathologic changes unremarkable angulated fibers of skeletal muscles
Histology of Pharynx inflammation and fibrosis chronic inflammation normal normal
Esophagus no pathologic changes T-lymphocyte infiltration of Auerbach's plexus no pathologic changes no pathologic changes
Larynx no pathologic changes ulceration with chronic and acute inflammation pink mucosa delicate pink mucosa
Lungs normal bronchopneumonia bilateral pneumonia pulmonary emboli
Thyroid normal normal cystic nodule filled with pink, amprphous material, consistent with goiter follicular adenomas
Ovaries no pathologic changes no pathologic changes small - microscopic fibrosis, no follicles covered by tumor
Uterus leiomyomas adenomyosis small - calcified nodules 1 cm, leiomyomas covered by tumor
Breasts fibrocystic changes fibrocystic changes no masses no masses
Cause of death XP-related neurologic degeneration XP-related neurologic degeneration Glioblastoma WHO grade IV. Tumor cells positive for GFAP and IDH1, negative for EGFR. P53 positive in <5% tumor cells. metastasis of well differentiated mucinous adenocarcinoma of uterine endocervix
  1. 1BCC - basal cell carcinoma, SCC -squamous cell carcinoma, MIS - melanoma in situ 2From Ramkumar et al. (reference 26) 3From Gaasterland et al. (reference 48) *Coriell Institute for Medical Research cell culture identification number **American Type Culture Collection cell culture identification number.