Activities of the Research Group for Comprehensive Research of Gene Mutation-related Rare and Intractable Diseases of the Skin within the Project for Research on Intractable Diseases of the Ministry of Health, Labor, and Welfare of Japan.

The Hashimoto Research Group for Comprehensive Research of Gene Mutation-related Rare and Intractable Diseases of the Skin is a contributor to the Project for Research on Intractable Diseases of the Ministry of Health, Labor, and Welfare (MHLW) of Japan. Our research group performs clinical research on 23 rare intractable genetic skin diseases that are classified into eight disease groups. Among the 23 diseases, 17 are mainly studied by our research group, and 6 diseases are studied in collaboration with other research groups.

Ocular manifestations of xeroderma pigmentosum: long-term follow-up highlights the role of DNA repair in protection from sun damage.

Objective: Xeroderma pigmentosum (XP) is a rare autosomal recessive disease caused by mutations in DNA repair genes. Clinical manifestations of XP include mild to extreme sensitivity to ultraviolet radiation resulting in inflammation and neoplasia in sun-exposed areas of the skin, mucous membranes, and ocular surfaces. This report describes the ocular manifestations of XP in patients systematically evaluated in the Clinical Center at the National Institutes of Health.

Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair.

Background: The frequency of cancer, neurologic degeneration and mortality in xeroderma pigmentosum (XP) patients with defective DNA repair was determined in a four decade natural history study.

Methods: All 106 XP patients admitted to the National Institutes of Health from 1971 to 2009 were evaluated from clinical records and follow-up.

Results: In the 65 per cent (n=69) of patients with skin cancer, non-melanoma skin cancer (NMSC) was increased 10,000-fold and melanoma was increased 2000-fold in patients under age 20.

Mental retardation, spasticity, basal ganglia calcification, cerebral white matter lesions, multiple endocrine defects, telangiectasia and atrophic skin: a new syndrome?

We report on an 8-year-old boy with mental retardation and spastic tetraparesis associated with atrophic skin on the face and extremities, telangiectasia, and severe dental caries. Basal ganglia calcification and multiple lesions in the subcortical white matter have been present since infancy. The patient has complications of liver dysfunction, multiple endocrine defects, and elevation of blood/cerebrospinal fluid lactate.

Heterozygous individuals bearing a founder mutation in the XPA DNA repair gene comprise nearly 1% of the Japanese population.

Individuals who are homozygotes for mutations in DNA repair genes are at high risk for cancer. It is not well documented, however, if the heterozygous carriers of the mutation are also predisposed to cancer. To address the issue, xeroderma pigmentosum (XP) in Japan is an interesting candidate because of three major reasons: XP is an autosomal recessive disorder with an enormously elevated risk of skin cancer, the frequency of XP patients is higher in Japan than in other parts of the world, and more than half of Japanese XP patients are homozygous for the same founder mutation in the XPA gene.

Two new XPD patients compound heterozygous for the same mutation demonstrate diverse clinical features.

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are both rare autosomal recessive disorders with defects in DNA repair. They are usually distinct both clinically and genetically but in rare cases, patients exhibit the clinical characteristics of both diseases concurrently. We report two new phenotypically distinct cases of XP with additional features of CS (xeroderma pigmentosum and Cockayne syndrome crossover syndrome (XP/CS)) carrying an identical mutation (G47R) in the XPD gene within the N terminus of the protein.

Decreased gene expression responsible for post-ultraviolet DNA repair synthesis in aging: a possible mechanism of age-related reduction in DNA repair capacity.

A reduction in the post-ultraviolet (UV) DNA repair capacity is associated with aging. To clarify the mechanism of this change, we examined the DNA repair capacity of skin fibroblasts from healthy donors of different ages by the two methods: host cell reactivation (HCR) assay and ELISA of cyclobutane pyrimidine dimers and pyrimidine-pyrimidone (6-4) photoproducts. In HCR assay, cells from elderly donors exhibited significant declines in the ability to restore transfected reporter DNA damaged by UV light.

UV dose measurements of photosensitive dermatosis patients by polycrystalline GaN-based portable self-data-acquisition UV monitors.

We have developed a UV monitor with polycrystalline (poly-) gallium nitride (GaN) UV sensors and evaluated its performance from the viewpoint of its effectiveness for use with photosensitive dermatosis patients. The poly-GaN UV sensor is sensitive to UV light from 280 to 410 nm even without optical filters. The UV monitor is a portable self-data-acquisition instrument with a minimum detection level (defined as average UV intensity over 290 to 400 nm) of 2 microW/cm2 and can store UV dose data for 128 days.