Ikirara insertions reveal five new Anopheles gambiae transposable elements in islands of repetitious sequence.

Characterization of Anopheles gambiae genomic clones containing Ikirara inverted repeats revealed five novel sequences related to known transposable elements (TEs). One TE is related to the mariner/Tc1 superfamily of class II (DNA-to-DNA) transposons, while four are related to class I (RNA-mediated transposition) elements. Crusoe, the class II element; is most similar to the Caenorhabditis elegans transposon Tc1-like TEs. Vash elements, represented twice in our clones, are related to the Q/T1 family of A. gambiae non-LTR retrotransposable elements. Guildenstern is a member of the RT1 and RT2 non-LTR retrotransposon family. Although RT1 and RT2 elements normally have a highly stereotyped insertion preference for sequences within ribosomal genes, Guildenstern is not located in ribosomal sequence. JuanAg is the first anopheline member of the mosquito non-LTR retrotransposon family of Juan elements that previously had included just the culicine elements JuanA and JuanC. Approximately 753 bp is missing from the central portion of the JuanAg reverse transcriptase gene, where an Ikirara inverted repeat is found in its stead. Ozymandias, the only LTR retrotransposon found in the clones, is most similar to the Drosophila melanogaster 412 element. Single Ikirara inverted repeats were also found adjacent to nontransposable element repetitious sequences. Our analysis suggests that the A. gambiae genome organization could best be described as islands of short-period interspersion repetitious DNA in a sea of long-period interspersion, mostly unique sequence DNA.

Double primary cancers of the breast and thyroid in women: molecular analysis and genetic implications.

Multiple primary cancers are characteristic of hereditary cancer syndromes. A familial association between breast and thyroid cancer has been suggested, but a genetic basis for this association has not yet been established. To determine the extent to which double primary cancers of the breast and thyroid are due to common hereditary factors, we conducted a registry- and hospital-based study in Ontario and Quebec. We obtained family histories of 74 women diagnosed with both cancer of the breast and thyroid before 70 years of age. Cancer histories were obtained for the 533 first- degree relatives of these women. The observed cancer rate in the relatives was compared with the expected number, based on age- standardized Canadian cancer incidence rates, and relative risks were estimated. A total of 87 cancers were observed in the relatives, compared to 93.7 expected cancers, giving a relative risk of 0.9 (95% confidence interval (CI): 0.7-1.1). The risk for breast cancer was 1.1 (95% CI: 0.6-1.7) and the risk for thyroid cancer was 0.7 (95% CI: 0-3.8). Blood samples were collected on 53 patients for mutational analysis of the BRCA1, BRCA2, and PTEN genes. One woman was found to be a carrier of a BRCA1 mutation (exon 11 3227delT). Our findings do not support the hypothesis that a significant proportion of double primary cancers of the breast and thyroid are due to hereditary factors.

Normal external genitalia in a female with classical congenital adrenal hyperplasia who was not treated during embryogenesis.

Classical congenital adrenal hyperplasia (CAH) results from an inherited enzymatic defect in cortisol synthesis and more than 90 per cent of cases are due to 21-hydroxylase deficiency. The androgen excess associated with this condition typically results in ambiguous external genitalia in affected females. It has been shown that prenatal treatment with dexamethasone is successful in preventing or reducing genital ambiguity in affected females. Rather than treating with dexamethasone, some couples choose to terminate the pregnancy when an affected fetus is prenatally diagnosed. We report a female with classical CAH who was born with normal external genitalia, although maternal treatment with dexamethasone did not begin until 16 weeks' gestation.

Pedigree analysis of French Canadian families with T14484C Leber's hereditary optic neuropathy.

We analyzed the clinical phenotype and determined the recurrence risks to relatives of patients with T14484C Leber's hereditary optic neuropathy (LHON). LHON is a maternally inherited optic neuropathy that primarily affects adolescent males. It is usually associated with one of three mtDNA mutations: G3460A, G11778A, or T14484C. Definition of recurrence risks for the T14484C mutation previously has not been possible due to the relative scarcity of families with this mutation. We obtained blood samples from index patients and their consenting family members, all of whom were of French Canadian ancestry and screened for LHON mutations in mtDNA. Referring ophthalmologists furnished clinical summaries and patients provided pedigree data. T14484C was the most common mutation in the pedigrees analyzed and was always homoplasmic. In these pedigrees, the ratio of affected males to females was 8:1. Median age at onset for males was 19 years (95th percentile, 40.8 years; range, 6 to 48 years). Some improvement of vision was observed in 58% of patients. Recurrence risks to brothers were 28%, sisters 5%, nephews 30%, nieces 3%, male matrilineal first cousins 19%, and female matrilineal first cousins 4%. Recurrence risks to brothers and nephews were not different; however, recurrence risks to brothers and male cousins and to nephews and male cousins were significantly different. There were no differences in recurrence risks to sisters and nieces or to either group compared with their female cousins. Affected females did not have more affected children than unaffected females. The clinical characteristics of French Canadian patients with T14484C LHON were strikingly similar to those in previous reports, suggesting that recurrence risks are generalizable to other T14484C LHON populations for genetic counseling of T14484C LHON families.