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A non-mosaic trisomy 20 was discovered in all cells in two separate cultures from an age-related genetic amniocentesis. Karyotypes of cells obtained via amniocentesis at the time of termination and of cells cultured from the placenta gave the same unambiguous results. However, the fetus, under macro- and microscopic analysis, showed only two minor anomalies: left simian crease and low-set ears. These findings are more suggestive of a normal or at most mosaic trisomy 20 state. The significance of this finding for prenatal diagnosis is discussed.

We report on a 6-year-old Caucasian boy with direct insertion of genetic material from the short arm of chromosome 4 to the short arm of chromosome 2. He was referred for evaluation because of global developmental delay and seizure disorder. A karyotype performed at 4 1/2 months of age, by a laboratory elsewhere, reportedly showed a deletion of chromosome 4(p12). When we saw him, he had macrocephaly, hypotonia, psychomotor retardation, multiple minor congenital anomalies, and EEG abnormalities. Repeat chromosomes performed by our laboratory revealed that his karyotype was 46,XY,dir ins(2;4)(p24;p15.3p13). Fluorescence in situ hybridization (FISH) analysis, using chromosomes 2 and 4 painting probes confirmed that material from 4p has been translocated to 2p. Also, FISH analysis using the Wolf-Hirschhorn critical region probe revealed that both loci are intact. Parental chromosomes were normal. This complex rearrangement, though it appears balanced, probably might have resulted in either a structural loss of genetic material or functional loss of a gene action. Thus, his phenotype could be explained by this de novo insertion of chromosome 4 material into chromosome 2. There is no reported case of this specific chromosome rearrangement.

The testis-specific histone H1t gene is known to be transcribed only in pachytene primary spermatocytes during spermatogenesis. Previous studies of the rat histone H1t gene revealed a unique promoter sequence element between the H1/GC box and the H1/CCAAT box. Proteins in crude nuclear extracts of rat testis bind specifically to this sequence element and a temporal correlation exists between the appearance of these DNA binding proteins and the onset of transcription. These discoveries led to a search for histone H1t genes in other mammalian species. The human and monkey histone H1t genes were amplified from genomic DNA using the polymerase chain reaction (PCR). The amplified genes were cloned and the genomic derived inserts were sequenced using linear PCR. Both proximal promoters contained the highly conserved H1/AC box, H1/CCAAT box, and H1/TATA box found in nongerminal H1 genes. Both promoters also contained the H1/GC box and the H1t/CCTAGG sequence element between the H1/GC box and H1/CCAAT box previously seen only in the H1t promoter. Specific amplification of the human H1t gene using template DNA samples from a NIGMS human/rodent somatic cell hybrid mapping panel has shown that the human histone H1t gene is located on chromosome 6.

The Women Health Initiative Clinical trial results suggest that post-menopausal women receiving estrogen + progesterone are at risk for heart disease compared with estrogen alone supplemented women. We examined the hypothesis that progesterone but not 17beta-estradiol (E) increases the secretion of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. U937 human monocytes were cultured with normal or high glucose in the presence and absence of estrogen or progesterone at 37 degrees C for 24 h. Results show that estrogen inhibits IL-6 but not TNF-alpha secretion (p0.05) in monocytes activated by lipopolysaccharide (LPS) or high glucose. In addition, progesterone increased the TNF-alpha secretion in activated monocytes. Thus, progesterone supplementation along with estrogen may increase blood levels of pro-inflammatory cytokine TNF-alpha and thus risk of heart disease in post-menopausal women.

We report on a 43-year-old woman who was referred for evaluation because of minor facial anomalies, myopathy, sterility, short stature, hearing loss, downward slant of palpebral fissures, bilateral ptosis, severe micro/retrognathia, high arched palate, and scoliosis. Cytogenetic analyses utilizing GTG/CBG bandings showed presence of one i(1p) and one i(1q) without normal chromosome 1 homologues. Fluorescence in situ hybridization analysis showed hybridization to only two chromosomes, consistent with the G-banded interpretation of i(1p) and i(1q). To the best of our knowledge, this is the first case of isochromosomes 1p and 1q replacing the two normal chromosome 1s. Molecular investigations using markers for chromosome 1 showed inheritance of only one set of paternal alleles and absence of any maternal alleles in the patient. The adverse phenotype of the patient may be due to one or more recessive mutations, genomic imprinting, or a combination of both.

Individuals in South Carolina with the Fragile X [ fra(X) ] or Martin-Bell syndrome have been ascertained by referral for evaluation of facial abnormalities, macroorchidism or mental deficit; by screening patients in residential and day programs for the mentally retarded; and by family follow up after an index case has been identified. Between 1982 and 1987, 100 positive fra(X) males were diagnosed. Of these, 35 were residents of residential facilities for the mentally retarded representing 2.5% of the population of institutionalized males. Another 23 were found in community day programs for the mentally retarded. Of these 58 cases, 28 (48%) were ascertained by screening for the craniofacial characteristics of the Martin-Bell syndrome, namely long face, midface hypoplasia, prominent forehead, large mandible and large simple pinnae. Although this screening procedure proved to be productive, it was found that the craniofacial traits of long face, midface hypoplasia, large jaw and simple pinnae were found less frequently in black fra(X) positive males and in prepubertal boys of both races.

We collected data on growth, psychomotor development, speech and language development, and intellectual function on a cohort of 100 males with the fragile X chromosome and 95 carrier females. The data include information on prenatal growth (33 males), growth during the preadult years (32 males), psychomotor development during the first 2 years (25 males), speech and language development (15 males and 5 females), and intellectual function (93 males, 33 females, and 10 obligate carriers who were cytogenetically normal). Birth measurements appeared normal when plotted on the Usher/McLean curves of newborn infants (mean head circumference - OFC - at 40th centile, length at 60th centile and weight at 55th centile). Following birth, OFC rose above the 50th percentile and continued above average throughout the preadult years, whereas average length was above average for the first 5 years only and weight did not deviate from the normal mean. Psychomotor development lagged behind the norm from birth with affected males requiring nearly twice as long as expected to sit alone, walk unassisted, and say first words clearly. All males and females studied had significant language delay; all except one male had abnormalities of articulation. All on whom a clear voice sample was obtained had low voice pitch, and 80% had a hoarse or harsh quality of voice. Five males had word repetitions or perseverative speech during the preadult years. The mean IQ of the 93 males studied was 33 and regression analysis demonstrated a decrease in intellectual performance with age. Four fifths of the female carriers who expressed the fra(X) had intellectual performance in the mentally retarded range and showed similar decrease in performance with age. Obligate female carriers who did not express the fra(X) site had normal IQs (IQ 102 +/- 13.3).

Cytogenetic and molecular analyses of three dicentric X chromosomes were performed in an attempt to identify the parental origin and mechanism of formation of the aberrant chromosomes. Results indicate that, in these three cases, the dicentric chromosomes were formed by chromatid breakage and reunion of sister chromatids at the breakpoint. In two cases the abnormal chromosomes were paternal in origin; in the third case the dicentric originated from the maternal X chromosome.

The gibbon Hylobates hoolock has been found to possess a karyotype different in diploid number and banding pattern from that of any other hylobatid. We propose that the hoolock gibbon occupy its own subgenus in the genus Hylobates.