Disease

Genetic defect

Cutaneous Findings

Xeroderma Pigmentosa

XPA

XPA gene 9q34.1. Zinc finger protein involved in DNA binding

Stage 1: Diffuse erythema, scaling, hyperpigmentation resembling freckles.

Stage 2: Atrophy, mottled pigmentation, telangiectasia. Multiple solar keratoses.

Stage 3: SCC, BCC, fibrosarcoma, melanoma.

XPB

The XPB and XPD gene products are part of a 9-subunit protein complex (TFIIH) that is also needed for the open complex formation. Helicase. Chromosome 2 (2q21)

XPC

DNA binding protein repair of non-transcribed regions (3p25.1)

XPD

The XPB and XPD gene products are part of a 9-subunit protein complex (TFIIH) that is also needed for the open complex formation. Also helicase c-some 19q13.2

XPE

Dimeric protein involved in recognition of damaged DNA 11q12-q13

XPF

The XPG and XPF genes encode endonucleases XPF gene product functions as an endonuclease when complexed to another protein

XPG

The XPG gene product is required for the open complex formation

XP-Variant

XP(A-G), h RAD 30. Defective ability to convert newly synthesized DNA from low –high molecular weight after UV radiation.

Cockayne

Type A:

CSA/ERCC8 acts on transcription-coupled repair (TCR) pathway. Mutation causes inablity to synthesize ribonucleic acid (RNA) after exposure to UV light.

Apparent after 1 year of age. Photosensitivity, thin dry hair, progeroid appearance.

Type B:

CSB/ERCC6 acts on transcription-coupled repair (TCR) pathway. Encodes helicase (involved in DNA unwinding)

Present at birth. Photosensitivity, thin dry hair, progeroid appearance.

Type C:

Xeroderma Pigmentosa–Cockayne syndrome (XP-CS)

Cockayne A/B in addition to XP manifestations

Bloom’s

BLM Band 15q26.1 DNA helicase – maintains genomic stability

Telangiectasias, photosensitivity

Muir-Torre

MLH1/MSH2 DNA mismatch repair genes

Sebaceous tumors, Keratoacanthoma, Gastrointestinal cancer