Uniform deletion junctions of complete azoospermia factor region c deletion in infertile men in Taiwan.

AIM: To determine the deletion junctions of infertile men in Taiwan with azoospermia factor region c (AZFc) deletions and to evaluate the genotype/phenotype correlation. METHODS: Genomic DNAs from 460 infertile men were examined. Bacterial artificial chromosome clones were used to verify the accuracy of polymerase chain reaction. Deletion junctions of the AZFc region were determined by analysis of sequence-tagged sites and gene-specific markers. RESULTS: Complete AZFc deletions, including BPY2, CDY1 and DAZ genes, were identified in 24 men. The proximal breakpoints were clustered between sY1197 and sY1192, and the distal breakpoints were clustered between sY1054 and sY1125 in all but one of the 24 men. The testicular phenotypes of men with complete AZFc deletion varied from oligozoospermia, to hypospermatogenesis, to maturation arrest. CONCLUSION: We identified a group of infertile men with uniform deletion junctions of AZFc in the Taiwan population. Despite this homogeneous genetic defect in the AZFc region, no clear genotype/phenotype correlation could be demonstrated.

Isochromosome of Yp in a man with Sertoli-cell-only syndrome.

OBJECTIVE: To address phenotype/genotype correlation in a man with i(Y)(p10). DESIGN: Case report. SETTING: University-based reproductive genetics laboratory. PATIENT(S): A 27-year-old azoospermic man with i(Y)(p10), relatively normal stature, and testicular Sertoli-cell-only syndrome. INTERVENTION(S): Testicular biopsy, cytogenetic study, Y-chromosome deletion mapping analysis, fluorescence in situ hybridization (FISH). MAIN OUTCOME MEASURE(S): Expression of Y-chromosome genes. RESULT(S): We have identified one azoospermic man with i(Y)(p10) of 312 Taiwanese men presenting with a severe spermatogenic defect. Y-chromosome deletion mapping analysis confirmed deletions of all Yq sequences, including a putative growth controlling gene. Fluorescence in situ hybridization (FISH) analysis showed duplication of Yp material. The patient had normal stature considering midparental height. He also had no germ cells in the testicular tissue (Sertoli-cell-only syndrome) resulting from the loss of azoospermia factor in Yq. CONCLUSION(S): Among structural rearrangements of the Y-chromosome, the isochromosome of Yp occurs very rarely. This case is the first reported case of an isochromosome Yp with a detailed description of testicular histology and body height.

Rapid and simple quantitative measurement of alpha-fetoprotein by combining immunochromatographic strip test and artificial neural network image analysis system.

BACKGROUND: Quantitative immunochromatographic strip (ICS) assay can facilitate clinical diagnosis by providing more information than traditional qualitative or semiquantitative strip assay. METHODS: We constructed a human serum alpha-fetoprotein (AFP) measurement system by combining semiquantitative ICS tests and artificial neural network (ANN) image analysis system [immunochromatographic strip analyzed by artificial neural network image analysis system (IAIS)]. After ICS tests completed, the AFP concentration can be obtained from analysis of IAIS software. The equipment required are commercial semiquantitative AFP dipstick, optical scanner, centrifuge (option), personal computer, and software of IAIS. RESULTS: The serum AFP concentrations measured by IAIS were strongly correlated (r = 0.9971) with that by RIA. Using Bland-Altman analysis, the IAIS achieved clinical acceptable limits of agreement in comparison with RIA. The within-run precision of IAIS, expressed as coefficients of variation (CV), at 81.7 ng/ml was 1.50% and, at 244.4 ng/ml, was 1.09%. The measurement of serum AFP by IAIS can be completed in 20 min. CONCLUSIONS: The newly constructed quantitative immunochromatographic strip assay (IAIS) is a simple, rapid, and reliable method for serum AFP measurement. With the simple equipment required, the IAIS can be performed outside the laboratory and is ideal for outpatient or point-of-care AFP testing.

Ultrasound estimation of fetal weight with the use of computerized artificial neural network model.

The aim of this study was to test if the computerized artificial neural network (ANN) model could improve ultrasound (US) estimation of fetal weight over estimation with the other commonly used formulas generated from regression analysis. First, as the training group, we performed US examinations on 991 singleton fetuses within 3 days of delivery. Six input variables were used to construct the ANN model: biparietal diameter (BPD), occipitofrontal diameter (OFD), abdominal circumference (AC), femur length (FL), gestational age and fetal presentation. Second, a total of 362 fetuses were assessed subsequently as the validation group. In this training group, the ANN model was better than the other compared formulas in fetal weight estimation (n = 991, mean absolute error 183.83 g, mean absolute percent error 6.02%, all p < 0.0001). In addition, the validation group further proved the results (n = 362, mean absolute error 179.91 g, mean absolute percent error 6.15%, all p < 0.005). In conclusion, the computerized artificial neural network (ANN) model could provide better US estimation of fetal weight than estimations by means of commonly used formulas generated from regression analysis.

Maternal uniparental disomy in a patient with Prader-Willi syndrome with an additional small inv dup(15) chromosome.

Prader-Willi syndrome (PWS) is a complex genetic disorder. About 70% of cases have a paternal deletion at 15q11-q13, and most of the remaining cases are caused by maternal uniparental disomy (UPD). In rare cases of PWS with maternal UPD, small marker chromosomes are identified. Patients with inv dup(15) are at an increased risk of developing PWS or Angelman syndrome (AS) due to UPD. They may be also at increased risk for developmental delay due to additional copies of genes located within the PWS/AS critical region. Therefore, molecular investigations in patients with a supernumerary marker chromosome (SMC) are necessary to provide proper genetic counseling. We report a female infant with central hypotonia, weak crying, feeding problems, failure to thrive, and developmental delay after birth. Chromosome analysis revealed an SMC in 55% of metaphase cells. Fluorescence in situ hybridization showed that this marker chromosome was constituted by a small isodicentric inverted duplication of chromosome 15 [inv dup(15)]. Microsatellite analysis showed uniparental isodisomy of maternal chromosome 15 in the proband. Diagnosis of PWS was further confirmed by methylation-specific polymerase chain reaction. The inv dup(15) marker chromosome was also of maternal origin. Follow-up at the age of 18 months revealed a height in the 10th percentile and weight in the 50th percentile. She had poor activity and muscle tone, and was unable to walk independently. There was no psychomotor retardation, behavior disturbance or seizure.

Interstitial deletion 11(p11.12p11.2) and analphoid marker formation results in inherited Potocki-Shaffer syndrome.

We report a family with inherited Potocki-Shaffer syndrome. The phenotypically normal mother has an interstitial deletion of 11(p11.12p11.2) with neocentric marker chromosome formation. The marker chromosome contains the deleted material on 11p11.2 and is likely a ring. The patient inherited a maternal deleted chromosome 11 but not the marker chromosome, thus resulting in an unbalanced karyotype along with the phenotype of Potocki-Shaffer syndrome. The deleted region in our case-11p11.12p11.2-is a newly reported site of constitutional neocentromere formation. This is also the first report describing deletion of 11p11.12-p11.2 and neocentromere formation resulting in inherited Potocki-Shaffer syndrome.

Ring (Y) in two azoospermic men.

We have identified two azoospermic men with r(Y) in 312 infertile men presenting with non-obstructive azoospermia or oligozoospermia. Their karyotypes were 45,X [9]/46,X, r(Y)(p11q11) [11] (case 1), and 46,X,r(Y)(p11q11) (case 2), respectively. In both cases, the Yp breakpoints were located within the pseudoautosomal region. Both cases had extensive deletions of azoospermia factors (AZFs). Case 1 also had deletion of the putative growth controlling gene (GCY) and the Yq breakpoint was located between sY741 and USP9Y. The Yq breakpoint was located between sY105 and sY109 in case 2. Both cases did not have Turner stigmata except short stature in case 1. By a combination of cytogenetic and molecular genetic tools, we showed r(Y) arose from breakage in both arms of the chromosome with subsequent fusion of two broken ends of the centric fragment to form a continuous ring. Spermatogenic defects in men with r(Y) may result from deletion of Y-linked AZFs combined with synaptic failure.

Prenatal diagnosis of holoprosencephaly in two fetuses with der (7)t(1;7)(q32;q32)pat inherited from the father with double translocations.

The presence of two independent translocations in one person is rare. Herein, we report the prenatal diagnosis of two sibling fetuses with holoprosencephaly, whose father is a carrier of double translocations. The karyotype of the father is 46,XY, t(1;7) (q32;q32), t(14,15) (q32.1;q26.3). The two fetuses had variable facial dysmorphisms and identical cytogenetic abnormality-a derivative (7) t(1;7) (q32;q32) inherited from the father. The proband 1 showed a small mouth, a single median eye and a proboscis above the eye, while the proband 2 showed hypotelorism, a flat nose, cleft lip and cleft palate. Both fetuses also had alobar holoprosencephaly. Haploinsufficiency of the sonic hedgehog gene at 7q36 does account for the occurrence of holoprosencephaly in the two fetuses with a deletion of distal 7q (7q32 --> qter).