Carrier frequency of the IVS4 + 4 A-->T mutation of the Fanconi anemia gene FAC in the Ashkenazi Jewish population.

Fanconi anemia (FA) is a genetically and phenotypically heterogeneous autosomal recessive disorder defined by a cellular hypersensitivity to DNA cross-linking agents. One of the FA genes, FAC, has been cloned and the genomic structure of the coding region has been characterized. We have developed amplification refractory mutation system (ARMS) assays for five known mutations in FAC, and have applied these assays to determine the carrier frequency of the IVS4 + 4 A-->T (IVS4) mutation in an Ashkenazi Jewish population. We tested 3,104 Jewish individuals, primarily of Ashkenazi descent, for the two most common FAC mutations, IVS4 and 322delG. Thirty-five IVS4 carriers were identified, for a carrier frequency of 1 in 89 (1.1%; 95% confidence interval 0.79% to 1.56%); no 322delG carriers were found. To determine if the IVS4 mutation was confined to the Ashkenazi Jewish population, we tested 563 Iraqi Jews for IVS4, and no carriers were found. Because the IVS4 mutation has only been found on chromosomes of Ashkenazi Jewish origin and is the only FAC mutation found on these chromosomes, we suggest that a founder effect is responsible for the high frequency of this mutation. With a carrier frequency greater than 1% and simple testing available, the IVS4 mutation merits inclusion in the battery of tests routinely provided to the Jewish population.

Skin response to ultraviolet B light in patients infected with human immunodeficiency virus.

Photosensitivity disorders have been reported in human immunodeficiency virus (HIV)-infected patients, often as the initial manifestation of the disease. The objective of this study was to evaluate whether the HIV-infected population demonstrates increased sensitivity to ultraviolet B (UVB) radiation. Minimal erythema dose values to UVB (MED-B) of 57 consecutive HIV-infected patients were compared to those of a control group of 57 consecutive patients with skin diseases, who were otherwise healthy and had no risk factors for HIV infection. MED-B determinations were performed in all individuals prior to the initiation of phototherapy for treatment of skin disease. None of the patients had a history of photosensitivity. Furthermore, the mean levels of the highest UVB doses received by each group during the treatment courses were compared. The mean age of the HIV-infected cohort was 43 years (range 26-61 years). The mean MED-B for this group was 82.8 +/- 3.8 (SEM) mJ/cm2. The mean age of the control group was 45 years (range 24-77 years), and their mean MED-B was 81.0 +/- 3.8 (SEM) mJ/cm2. After 12 weeks of treatment, one HIV-infected patient developed photosensitivity associated with a decreased MED-B value. The mean level of the highest UVB doses received by the HIV-infected group [427.5 +/- 67.2 (SEM) mJ/cm2] was lower than that received by the control group [640.8 +/- 65.9 (SEM) mJ/cm2], since HIV-infected patients received fewer treatments (mean: 34.7 treatments per patient) than the patients in the control group (mean: 65.6 treatments per patient). These data indicate that the HIV-infected patient population, without history of photosensitivity, does not show increased sensitivity to UVB light as determined by MED-B values.