Complex rearrangements of Y chromosome suggest RPS4Y1 as lymphedema candidate gene.

OBJECTIVE: Cystic hygromas are frequently encountered in fetus with Turner syndrome (TS). Nevertheless, identification of genetic loci responsible for the cystic hygroma has been problematic. Here, we tried to elucidate the candidate gene for cystic hygroma through a rare case of complex Y chromosomal rearrangements involving duplication of partial Yq and monosomy of partial Yp. CASE REPORT: A 30-year-old woman, gravida 1 para 0, was diagnosed with fetal cystic hygroma at 12 weeks of gestation. The genetic analysis of the product of conception revealed complex rearrangement of Y chromosome: microdeletion in Yp11.2p11.31 and microduplicatin in Yq11.223q11.23. The deleted region spans about 6.25 Mb and includes 76 genes, including SRY. The duplicated region spans about 4.76 Mb and includes 145 genes. CONCLUSION: From this rare case with non-mosaic complex Y-chromosome rearrangements, we could narrow down Turner stigmata critical region to Yp11.2～p11.3. We also propose RPS4Y1 as lymphedema candidate gene.

A non-mosaic isodicentric Y chromosome resulting from breakage and fusion at the Yq pseudo-autosomal region in a fetus.

The dicentric Y chromosomes are the most commonly found in the structural aberration of Y chromosome. If the dicentric chromosome has completely symmetric arms, it is considered an isodicentric chromosome. The sites of breakage and fusion at Yp and Yq are variable, but breakage and fusion at the pseudo-autosomal region has never been reported. Herein we reported identification de novo isodicentric (Yq12) in a fetus. The fusion occurred at Yq pseudo-autosomal region very close the telomere and resulted in duplication of Y chromosome. The baby was grossly normal at birth. In conclusion, isodicentric Y chromosome could result from breakage and fusion at the Yq pseudo-autosomal region.

A family with Xq22.3q25 interstitial deletion and normal ovarian function.

OBJECTIVE: To investigate genomic changes in a family with deletion of X chromosome q22.3-q25 associated with normal constitutional and reproductive phenotypes. DESIGN: Case report. SETTING: Academic district hospital genetic laboratory. PATIENT(S): A family incidentally found to have deletion of X chromosome q22.3-q25. INTERVENTION(S): Cytogenetic analysis and array-based comparative genomic hybridization for amniotic fluid and peripheral blood lymphocyte of family members. MAIN OUTCOME MEASURE(S): Ovarian function and menstrual cycles. RESULT(S): The proband and two daughters showed deletion of Xq22.3q25. This region spans 17.4 Mb and contains 121 genes. CONCLUSION(S): Female subjects with deletion of Xq22.3q25 may present with normal constitutional and reproductive phenotypes.

Simultaneous use of mifepristone and misoprostol for early pregnancy termination.

OBJECTIVE: Simultaneous mifepristone 200mg and vaginal misoprostol 800µg produces a complete abortion rate of approximately 90% at up to 63 days of gestation. The aim of this study was to determine the effectiveness of concurrent administration of mifepristone 200mg and vaginal misoprostol 600µg with respect to early medical abortion. MATERIALS AND METHODS: A total of 254 women with undesired pregnancies of less than 49 days of gestation were enrolled. All women received oral mifepristone 200mg and vaginal misoprostol 600µg concurrently. Follow-up assessment by transvaginal ultrasonography was performed 3 days and 2 weeks after treatment. RESULTS: Efficacy outcome was analyzed for 242 women (95.3%) after excluding 12 individuals lost to follow-up. The complete abortion rate was 92.6%. The mean induction to abortion interval was about 5.8hours. The mean bleeding duration was about 12.6 days. The women indicated that the side effects were tolerable and 90% of them said that their experience was satisfactory. CONCLUSION: Concurrent administration of oral mifepristone 200mg and vaginal misoprostol 600µg is an efficacious regimen for medical abortion of pregnancies up to 49 days of gestation.

Quantitative trait analysis suggests polymorphisms of estrogen-related genes regulate human sperm concentrations and motility.

BACKGROUND: Human spermatogenesis is regulated by complex networks, and estrogens are recognized as one of the significant regulators of spermatogenesis. We tested the associations between variants of estrogen-related genes and semen parameters. METHODS: We performed genotyping for genetic variants of estrogen-related genes and quantitative trait analysis of fertile and infertile men with well-characterized reproductive phenotypes. Men with known semen parameters (n= 677) were enrolled, including 210 fertile men and 467 infertile men. A total of 17 genetic markers from 10 genes, including 2 estrogen receptors (ER-α, ER-ß), 7 estrogen synthesizing/metabolizing genes (CYP19A1, HSD17B1, CYP1A1, CYP1B1, COMT, GSTM1, GSTT1) and 1 transport gene (SHBG) were genotyped. Sperm concentration, motility and morphology were taken as quantitative traits to correlate with genetic variants in the estrogen-related genes. RESULTS: Five genes (rs1801132 and rs2228480 of the ER-α gene, rs1256049 and rs4986938 of the ER-ß gene, rs605059 of the HSD17B1 gene, rs1799941 of the SHBG gene and rs1048943 and rs4646903 of the CYP1A1 gene) were found to be significantly associated with sperm concentration (P< 0.01), while five genes (rs1801132 of the ER-a gene, rs1256049 of the ER-ß gene, rs1048943 of the CYP1A1 gene, rs605059 of the HSD17B1 gene and rs1799941 along with rs6259 of the SHBG gene) were associated with sperm motility (P< 0.01). None of the estrogen-related genes were associated with sperm morphology. With an increasing number of risk alleles, sperm concentration and motility tended to deteriorate and show a loci-dosage effect. CONCLUSIONS: Quantitative trait analysis based on a limited number of genetic markers suggests that estrogen-related genes mainly regulate sperm concentration and motility.

Association of USP26 haplotypes in men in Taiwan, China with severe spermatogenic defect.

AIM: To complete comprehensive haplotype analysis of USP26 for both fertile and infertile men. METHODS: Two hundred infertile men with severe oligospermia or non-obstructive azoospermia were subjected to sequence analysis for the entire coding sequences of the USP26 gene. Two hundred men with proven fertility were genotyped by primer extension methods. Allele/genotype frequencies, linkage disequilibrium (LD) characteristics and haplotypes of fertile men were compared with infertile men. RESULTS: The allele frequencies of five single nucleotide polymorphisms (370-371insACA, 494T>C, 576G>A, ss6202791C>T, 1737G>A) were significantly higher in infertile patients than control subjects. The major haplotypes in infertile men were TACCGA (28% of the population), TGCCGA (15%), TACCAA (8%), TGCCAA (6%), TATCAA (5%) and CATCAA (5%). The major haplotypes for the control subjects were TACCGA (58% of the population), CACCGA (7%), CATCGA (6%) and TGCCGA (5%). Haplotypes TGCCGA, TATCAA, CATCAA, CATCGC, TACCAA and TGCCAA were over-transmitted in patients with spermatogenic defect, whereas haplotypes TACCGA, CACCGA, and CATCGA were under-transmitted in these patients. CONCLUSION: Some USP26 alleles and haplotypes are associated with spermatogenic defect in the Han nationality in Taiwan, China.

High-dose misoprostol as an alternative therapy after failed medical abortion.

OBJECTIVE: The aim of this study was to determine the complete abortion rate for the vaginal administration of high-dose misoprostol after a failed medical abortion. MATERIALS AND METHODS: When their medical abortions failed after the conventional oral administration of mifepristone and misoprostol, participants then received 1,000 microg of misoprostol vaginally. The efficacy and side effects of this treatment were evaluated. RESULTS: Twenty-seven women who failed to abort after the conventional administration of mifepristone and misoprostol were enrolled in this trial. Fourteen days after the vaginal administration of 1,000 microg misoprostol, the overall complete expulsion rate had reached 88.8% (24/27). Most adverse effects were mild to moderate and did not require treatment. CONCLUSION: The vaginal administration of 1,000 microg misoprostol as a salvage therapy after a failed medical abortion appears to be a safe and highly effective alternative to surgical intervention.

Maternal derivative chromosome 9 and recurrent pregnancy loss.

OBJECTIVE: To disclose the relationship between a derivative chromosome 9 and recurrent pregnancy loss. DESIGN: Case report. SETTING: Referral from primary clinical care to tertiary hospital for further intervention. PATIENT(S): A 31-year-old woman who had four recurrent early spontaneous abortions. INTERVENTION(S): Cytogenetic and fluorescence in situ hybridization analyses of the chromosome harvested from peripheral blood sample. MAIN OUTCOME MEASURE(S): Karyotype of the patient. RESULT(S): The patient has a unique derivative chromosome 9, der(9)(9qter-->9p24::9p24-->9p11::9p13-->9qter). ish der(9) (CEP9x1,43N6x1,D9Z3x1). CONCLUSION(S): Maternal derivative chromosome 9 may cause recurrent pregnancy loss.

Efficacy of treating abdominal wall pain by local injection.

OBJECTIVE: When a patient's chief complaint is lower abdominal pain, but physical and ultrasonic examinations and laboratory tests show no evidence of any noticeable disease, physicians may make a wrong diagnosis, such as abdominal adhesion, chronic pelvic inflammatory disease, pelvic congestion and even psychosomatic disorders. In actuality, the pain may originate from the abdominal wall instead of the viscera. Local anesthetics coupled with steroid injections not only effectively alleviate the pain but also means that laparoscopy and medication can be avoided and is thereby worthy of wide use. Here, we present the results for the treatment of abdominal wall pain by local injection. MATERIALS AND METHODS: Between January 1994 and December 2005, we treated 211 abdominal wall pain patients. Diagnoses were based on the pressure of the abdominal wall tender point, which elicited sharp shooting pain during compression, and presence of positive Carnett's sign. After confirmation of the trigger point, a fine needle was used to inject a mixture of 0.5% bupivacaine 2 mL, 2% lidocaine 3 mL and 4 mg betamethasone 1 mL. The patients were examined on a weekly basis and underwent reinjection if symptoms recurred. RESULTS: There were 71 patients who were lost to or refused treatment or follow-up; the 140 remaining patients were evaluated. After trigger point injection in these patients, 95 (67.9%) reported no pain at all after treatment. Forty-five (32.1%) patients still had abdominal pain and required a second injection. A total of 133 (95%) patients showed complete pain resolution. After 3 months of follow-up, 115 (86.5%) patients remained free of abdominal pain. CONCLUSION: Local injection for selective abdominal wall pain patients produces significant pain relief. The diagnosis of abdominal wall pain is an important component in avoiding unnecessary operations in patients with abdominal pain.

Cytogenetic surveillance of mentally-retarded school children in southern Taiwan.

BACKGROUND AND PURPOSE: Mental retardation (MR), defined as having an IQ of less than 70, is present in approximately 2 to 3% of the population. Data on chromosomal abnormalities, an important cause of MR, are limited in the Taiwanese literature. This study evaluated the frequency and pattern of chromosomal abnormalities in school children with MR in southern Taiwan. METHODS: Peripheral blood samples of 419 children were collected from November 1999 to January 2003. Those with Prader-Willi syndrome (PWS), Angelman syndrome (AS) or fragile-X syndrome were excluded from the study. Metaphase chromosome preparations were obtained from peripheral blood cultures, and trypsin-giemsa (GTG) banded chromosomes were examined at the level of 500 to 600 bands. Fluorescence in situ hybridization was done for cases whose karyotypes could not be determined by conventional cytogenetic analysis. RESULTS: Of the 419 enrollees with MR, 10 had mild MR, while most had moderate to profound MR. Chromosomal abnormalities were found in 22.43% of the cases, with trisomy 21 being the major chromosomal abnormality, occurring in 77 cases (18.38%, 77/419 cases). Sex chromosome aneuploidies were found in 3 cases (0.72%, 3/419 cases). Structural abnormalities of autosomes were found in 13 cases (3.10%, 13/419 cases), including deletion, markers, unbalanced translocations, and inversions. One subject was found to have monosomy 20 mosaicism (0.24%, 1/419). CONCLUSIONS: Chromosomal abnormalities occurred in a high proportion of mentally retarded school children from southern Taiwan, with trisomy 21 being the most prevalent. These findings indicate the need for increased attention to prenatal, perinatal and postnatal screening in this population.