Two of four siblings expressed the salt-losing form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) and had identical human lymphocyte antigen (HLA) and complement C4 (fourth component of complement) types (HLA-A3,C4,B35,C4A3,C4BQO,DR1/A2,C-,B18,C4A3, C4BQO,DR6). The father and one unaffected sibling were heterozygous carriers of CAH, as determined by a 30-min iv ACTH stimulation test and HLA typing. In addition, the iv ACTH stimulation test revealed that the mother and the other unaffected sibling also carried an allele for an attenuated form of CAH. Restriction endonuclease digests of genomic DNA obtained from members of this family and from normal unrelated subjects were hybridized with cDNA probes encoding human 21-hydroxylase and C4. With the 21-hydroxylase probe, Southern blots prepared from control DNA samples revealed two major restriction fragments in each of four restriction endonuclease digests; TaqI produced major bands at 3.7 and 3.2 kilobases (kb), KpnI at 4.0 and 2.9 kb, EcoRI at 18 and 13 kb, and BglII at 15 and 12.5 kb. Southern blots prepared from DNA of the two patients lacked the 3.7-kb TaqI and 2.9-kb KpnI fragments, but had increased hybridization intensity (relative to control DNA samples) in the 3.2-kb TaqI and 4.0-kb KpnI fragments. By contrast, blots with EcoRI or BglII had two large hybridization fragments not different from control DNA samples. These data indicate the presence of two different 21-hydroxylase genes. Additional mapping studies revealed that the two genes had the restriction pattern of the inactive 21-hydroxylase gene. When genomic DNA that had been isolated from all members of this family and from normal subjects was hybridized with the human C4 cDNA probe, the restriction fragment hybridization patterns for all four endonuclease digests were similar in the two groups. Hence, our results suggest that the 21-hydroxylase deficiency of our patients is due to conversion of the active 21-hydroxylase gene to the inactive gene. This gene conversion was associated with absence of functional C4B protein, without any detectable alterations in the restriction fragment pattern of the C4 genes.
A CA that integrates multiple domains of professional competence is feasible, useful to students, and fosters reflection and change. Preliminary data suggest that this format is reliable and valid.
This study supports CSII as a safe and effective alternative to managing T1DM, with no increase in hypoglycemia and a trend to improve control, even in the youngest patients.
One morphologic feature of Turner syndrome is increased numbers of melanocytic nevi; however, little attention has been given to their characterization. The development of a melanoma in one of our patients with Turner syndrome prompted this study. We prospectively examined 10 patients with the disease, confirmed by karyotype. All patients underwent full body skin examination noting the number, size, distribution, and degree of clinical atypia of melanocytic nevi. Representative and unusual lesions were photographed. An average of 115 nevi were seen, with the majority measuring 1 to 5 mm. Most were located on the back and extremities. Clinical atypia was uncommon. Our patients had larger numbers of benign-appearing nevi than the general population. Large numbers of melanocytic nevi is a risk factor for melanoma, suggesting that these patients have an increase in one risk factor. Longitudinal studies are indicated to clarify this issue; nevertheless, we recommend periodic skin examinations and the regular use of sunscreens for individuals with Turner syndrome.
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