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Unexpected occurrence of xeroderma pigmentosum in an uncle and nephew
Stéphanie Christen-Zaech1, Kyoko Imoto, Sikandar G Khan
1Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Background:
Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by a decreased ability to repair DNA damaged by UV radiation and the early development of cutaneous and ocular malignant neoplasms. Approximately 20% of patients with XP also develop progressive neurologic degeneration.
Observations:
We describe a boy who was found to have XP after a severe burn following minimal sun exposure. His maternal uncle, now age 20 years, had been diagnosed with XP after a similar sunburn in infancy. The uncle has the typical skin pigmentary findings of XP along with severe progressive neurologic involvement. Although the infant's parents were not known to be blood relatives, the infant and his affected uncle proved to be compound heterozygotes for the same 2 frameshift mutations in the XPA DNA repair gene (c.288delT and c.349_353del). After the diagnosis of XP in the infant, genealogic investigation identified a common Dutch ancestor for both of his grandfathers 5 generations back.
Conclusions:
Counseling families at risk for a rare inherited disease is not always straightforward. The sociocultural and demographic backgrounds of the families must be considered for evaluation of risk assessment.
Insights
Xeroderma pigmentosum (XP) is a rare genetic disorder affecting DNA repair. This case highlights complex family genetics and the need for careful risk assessment in inherited diseases.
Area of Science:
- Genetics
- Molecular Biology
- Dermatology
Background:
- Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder.
- XP is characterized by impaired DNA repair after UV damage, leading to skin and eye cancers.
- Neurologic degeneration affects approximately 20% of XP patients.
Observation:
- A boy diagnosed with XP after severe sunburn following minimal sun exposure.
- His maternal uncle, also diagnosed with XP, presented with similar symptoms and progressive neurologic involvement.
- Both individuals were compound heterozygotes for two frameshift mutations in the XPA DNA repair gene.
Findings:
- Identified two specific frameshift mutations (c.288delT and c.349_353del) in the XPA gene.
- Genealogic investigation revealed a common ancestor for the patient and his affected uncle.
- Confirmed compound heterozygosity for the same mutations in both affected family members.
Implications:
- Family genetic counseling for rare inherited diseases requires careful consideration of sociocultural and demographic factors.
- Accurate risk assessment is crucial for families with a history of rare genetic disorders like XP.
- Understanding complex inheritance patterns aids in genetic counseling and patient management.
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