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Different subtypes of multiple endocrine neoplasia type 2 (MEN-2) appear to be linked to specific gene mutations in the RET oncogene. MEN-2 is characterized by tumors in various glands, including the thyroid and adrenals. It has three subtypes depending on the organs affected by tumors: MEN-2A, MEN-2B and familial medullary thyroid cancer (FMTC). Researchers performed genetic testing on 477 families worldwide who had a family history of MEN-2. A gene mutation at position 634 in the RET oncogene was associated with MEN-2A, while a mutation at position 918 was specific for MEN-2B and mutations at 768 and 804 were specific for FMTC., Objective.--Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder. The 3 recognized subtypes include MEN 2A, characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (pheo), and hyperpara-thyroidism (HPT); MEN 2B, by MTC, pheo, and characteristic stigmata; and familial MTC (FMTC), by the presence of MTC only. The purpose of this study was to establish the relationship between specific mutations and the presence of certain disease features in MEN 2 which could help in clinical decision making. Design.--Correlative survey study of 477 MEN 2 families. Setting.--Eighteen tertiary referral centers worldwide. Patient$.--A total of 477 independent MEN 2 families. Main Outcome Measures.--Association between the position and type of germline mutation in the RET proto-oncogene and the presence or absence of MTC, pheo, HPT, and/or other features in a family. Results.--There is a statistically significant association between the presence of any mutation at a specific position (codon 634) and the presence of pheo and HPT. The presence of a specific mutation, CGC at codon 634, has yet to be associated with FMTC. Conversely, mutations at codons 768 and 804 are thus far seen only with FMTC, while codon 918 mutation is MEN 2B--specific. Rare families with both MEN 2 and Hirschsprung disease were found to have MEN 2--specific codon mutations. Patients with Hirschsprung disease presenting with such mutations should be monitored for the possible development of MEN 2 tumors. Conclusions.--This consortium analysis suggests that genotype-phenotype correlations do exist and, if made reliably absolute, could prove useful in the future in clinical management with respect to screening, surveillance, and prophylaxis, as well as provide insight into the genetic effects of particular mutations. JAMA. 1996;276:1575-1579

A lack of uniformity in practices was revealed in a survey of laboratories offering screening for cystic fibrosis mutations. Forty-three laboratories responded, covering most of those offering such tests. The number of mutations screened for ranges from one to 70, with a median of about 12-14 mutations. Definite guidelines for specific mutations and minimal test panel sensitivities relative to ethnic populations being tested would be beneficial.

Background: Maximizing the accuracy of human papillomavirus (HPV) detection from a single sample is important for clinical and research purposes. The purpose of this study was to determine whether cyclic hormonal variation, recent sexual intercourse, interval between samplings, and the technique used to sample affect the detection of HPV.Methods: This study was a prospective, longitudinal, randomized controlled trial. Three techniques for self-sampling (2 consecutive synthetic polyester fiber [Dacron] swabs, a single Dacron swab, and a tampon) were repeated at 3 different sampling times during a period of 4 to 6 weeks in addition to 1 clinician-directed sampling of the ectocervix and endocervix at the first sampling time. All self-samplings were taken in a proscribed randomized order. Women (aged 18 to 68 years) attending a colposcopy clinic for abnormal cytology or abnormal cervical appearance participated in the study. The outcome measure was the detection of HPV by polymerase chain reaction amplification.Results: The 103 participants provided 1,189 cervicovaginal samplings. Logistic regression indicated that intercourse within 48 hours of sampling did not result in a greater detection of high-risk or any HPV type (odds ratio [OR] = 1.05, 95% confidence interval [CI], 0.65-1.69; OR = 1.08, 95% CI, 0.73-1.60, respectively). Among those women who have regular menstrual cycles, there was no cyclic effect on HPV detection for high-risk and any HPV types. Time from previous sampling did not affect HPV detection. Among the self-sampling techniques, using a single self-swab and the tampon resulted in the detection of HPV between 10% and 35% less often than using 2 consecutive swabs (P < .025). Self-sampling with 2 swabs was not significantly different from clinician sampling for detecting high-risk HPV types (OR for self-sampling = 0.87 (95% CI, 0.66-1.13)).Conclusions: HPV detection is not dependent on menstrual cycle timings, the recency of intercourse, or the time between samplings, but it is dependent on the sampling technique. [ABSTRACT FROM AUTHOR]