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Pao-Lin Kuo

Publications and source records attributed to Pao-Lin Kuo.

At least 37 records · Page 2Linked to original sources
PubMed2004

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.

Adult↗
PubMed2004

Expression profiles of the DAZ gene family in human testis with and without spermatogenic failure.

OBJECTIVE: To determine the expression profiles of the DAZ gene family in men with and without spermatogenic failure. DESIGN: Prospective case study. SETTING: University-based reproductive clinics and genetics laboratory. PATIENT(S): Thirty-four infertile men presenting with azoospermia. INTERVENTION(S): The mRNA transcript concentrations of the DAZ family genes (BOULE, DAZL, DAZ) and the housekeeping GAPDH gene in the testes of azoospermic men were examined by quantitative competitive-reverse transcription-polymerase chain reaction (QC-RT-PCR). The steady-state concentrations of mRNA encoding for each gene in each testicular sample were normalized by the amounts of GAPDH. MAIN OUTCOME MEASURE(S): Transcript ratios (gene/GAPDH) of BOULE, DAZL, and DAZ. RESULT(S): The transcript ratios for BOULE, DAZL, and DAZ were significantly decreased in tissues with spermatogenic failure (hypospermatogenesis, maturation arrest, and Sertoli cell-only). However, the ratios of BOULE/DAZL and DAZ/DAZL did not reveal any significant difference in all tissues. Three patients with DAZ deletion possess lower transcripts of BOULE and DAZL. CONCLUSION(S): All members of the DAZ gene family play important roles in human spermatogenesis. Decreased concentrations of DAZ family members in men with spermatogenic failure may be due to the secondary effect of germ cell loss, and transcriptional control of BOULE, DAZL, and DAZ are not altered in the various degrees of spermatogenic failure. Although the sample size is limited, no compensatory increase of DAZL or BOULE transcription was found in men with DAZ deletion.

Case-Control Studies↗
PubMed2004

Mechanism of recurrent spontaneous abortions in women with mosaicism of X-chromosome aneuploidies.

OBJECTIVE: To investigate the mechanism of recurrent miscarriages in women with mosaicism of X-chromosome aneuploidies. DESIGN: Prospective case-control study. SETTING: University-based reproductive clinic housed in a medical center with genetic laboratories. PATIENT(S): Eighteen women who experienced recurrent miscarriages and had mosaicism of X-chromosome aneuploidies; two control groups, one with a balanced structural autosomal rearrangement and the other without chromosomal abnormalities. INTERVENTION(S): Criteria were established for the diagnosis of low-grade X-chromosome mosaicism by using peripheral blood lymphocytes. Patients were evaluated for the pathogenesis of recurrent miscarriages. Their abortion rate was assessed, and each abortus was karyotyped. MAIN OUTCOME MEASURE(S): Abortion rate and karyotype of the abortus. RESULT(S): In comparison with patients with X-chromosome mosaicism with a balanced structural autosomal rearrangement, patients with X-chromosome mosaicism without a balanced autosomal structural rearrangement had a significantly higher incidence of diminished ovarian reserve (DOR) and had a somewhat higher prevalence of uterine anomalies. In comparison with controls without chromosomal abnormalities, the patients with a balanced autosomal structural rearrangement also had higher incidence of both conditions, but the differences were not statistically significant. At least two factors are implicated in recurrent miscarriages in women with X-chromosome mosaicism. Among them, DOR is the most prevalent (occurring in 44.4% of cases), followed by uterine anomalies (16.7% of cases). Cases with DOR had a higher abortion rate than did those without (68.6% vs. 44.1%). Cases with DOR also had a slightly higher rate of abnormal karyotypes in the abortus than did those without (73.7% vs. 42.9%). CONCLUSION(S): The oocytes of women with X-chromosome mosaicism are in a suboptimal state of development and are prone to embryonic lethality.

Abortion, Habitual↗
PubMed2004

Transcriptional levels of four Y chromosome-linked AZF genes in azoospermic men and their association with successful sperm retrieval.

OBJECTIVES: To investigate the transcriptional levels of four azoospermia factor genes in the testis of azoospermic men and to investigate the association between transcriptional levels and the results of sperm retrieval. METHODS: Thirty-eight azoospermic men with normal karyotype and without Y chromosome gene deletions were enrolled. The amounts of USP9Y (ubiquitin specific protease 9, Y chromosome), DBY (dead box on the Y), RBMY1 (RNA-binding motif on the Y, 1), and DAZ (deleted in azoospermia) transcripts were examined by quantitative competitive-reverse transcriptase-polymerase chain reaction. The steady-state concentrations of mRNA encoding for each gene in each testicular sample were normalized by the amounts of a housekeeping gene (glyceraldehyde phosphate dehydrogenase [GAPDH]). Differences in the transcript ratios (gene transcript/GAPDH transcript) among patients with different testicular histologic findings (normal spermatogenesis, hypospermatogenesis, maturation arrest, Sertoli cell-only syndrome) were analyzed. For each gene, the association between the transcript ratios and the results of sperm retrieval was evaluated. RESULTS: No statistically significant difference was found in the transcript ratios of USP9Y and DBY among the four histologic patient groups (P = 0.33 and P = 0.21, respectively). In contrast, statistically significant decreases were found in the transcript ratios of RBMY1 and DAZ in patients with spermatogenic failure (P = 0.0002 and P = 0.002, respectively). The transcript ratios of USP9Y and DBY were not associated with the results of sperm retrieval, and the transcript ratios of RBMY1 and DAZ revealed a positive association with successful sperm retrieval. CONCLUSIONS: The decreased transcriptional levels of RBMY1 and DAZ in patients with spermatogenic failure may reflect the generalized loss of germ cells. The transcriptional levels of RBMY1 and DAZ may have the potential of becoming useful parameters in the prediction of successful sperm retrieval.

Adult↗
PubMed2004

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.

Child↗
PubMed2004

Russell-Silver syndrome: molecular diagnosis of maternal uniparental disomy of chromosome 7 using methylation-specific polymerase chain reaction assay and single nucleotide polymorphisms genotyping.

Russell-Silver syndrome (RSS) should be suspected in patients with prenatal and postnatal growth retardation. Because there is no clinical feature specific for RSS, molecular analysis is necessary to confirm the diagnosis. Recently, maternal uniparental disomy of chromosome 7 (mUPD7) has been reported in approximately 10% of RSS patients. We describe a 10-year-old Taiwanese RSS girl with prenatal and postnatal growth retardation, relative macrocephaly, a triangular face, frontal bossing, and mild fifth finger clinodactyly. Molecular diagnosis of mUPD7 was confirmed by use of methylation-specific polymerase chain reaction and haplotype analysis with single nucleotide polymorphisms (SNPs) genotyping. Analyzing the methylation status of the PEG1/MEST gene is a cost-effective screening method for mUPD7 molecular diagnosis. However, positive cases should be subsequently confirmed by haplotype analysis using SNPs genotyping or short tandem repeat markers.

Child↗
PubMed2004

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.

Adult↗
PubMed2003

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).

Abnormalities, Multiple↗
PubMed2003

Placental sonolucency and pregnancy outcome in women with elevated second trimester serum alpha-fetoprotein levels.

BACKGROUND AND PURPOSE: Women with unexplained elevation of serum alpha-fetoprotein (AFP) are at increased risk for adverse pregnancy outcomes, including small for gestational age neonate, preterm labor, abruptio placentae, preeclampsia, intrauterine fetal death, and congenital malformations. This study investigated the association between placental sonolucency, elevation of maternal serum AFP, and pregnancy outcomes. METHODS: Singleton pregnancies (n = 168) with second trimester serum AFP level >/= 2.0 weight-adjusted multiples of the median (MoM) were recruited as the study group. Women with second trimester serum AFP level between 0.4 and 2.0 weight-adjusted MoM (n = 150) served as controls. A maternal Kleihauer-Betke stain was obtained for all participants. All participants were prospectively evaluated and the pregnancy complications were assessed by chart analysis after delivery. RESULTS: Compared with control subjects, women with placental sonolucent areas were not at increased risk for pregnancy complications, while women without sonolucent areas had higher risk of pregnancy complications. Singleton pregnancies with elevated serum AFP level had increased incidence of feto-maternal hemorrhage when placental sonolucency was observed. CONCLUSIONS: Our data suggest that feto-maternal hemorrhage may be the major factor contributing to elevated maternal serum AFP levels in pregnancies carrying placental sonolucencies. Screening for pregnancies with both elevated serum AFP and placental sonolucencies would help to identify the low-risk cases and facilitate cost-effective obstetric management.

Adult↗
PubMed2003

De novo 4p-syndrome with oligohydramnios sequence.

4p-syndrome, or Wolf-Hirschhorn syndrome, is associated with a deletion of chromosome 4p16.3 and involves multiple malformations that result in delayed growth and development and also facial dysmorphism. We report a case of Wolf-Hirschhorn syndrome in a female infant with a 4p deletion, for which the breakpoint was detected at p14. This patient had bilateral renal hypoplasia resulting from the oligohydramnios sequence (Potter syndrome), including characteristic facial abnormalities, deformed limbs, and pulmonary hypoplasia. Patent ductus arteriosus, ascites, and bilateral renal hypoplasia were noted. The patient had frequent pulmonary infections and died when she was 39 days old.

Abnormalities, Multiple↗
PubMed2002

Gene-based screening for Y chromosome deletions in Taiwanese men presenting with spermatogenic failure.

OBJECTIVE: To develop a simple and rapid protocol for detecting deletions of the Y chromosome and to evaluate the feasibility of gene-based screening in men with spermatogenic failure. DESIGN: Prospective case study. SETTING: University-based reproductive clinics and genetics laboratory. PATIENT(S): Two hundred two infertile men presenting with severe oligozoospermia and nonobstructive azoospermia. INTERVENTION(S): Fifteen gene-specific primers were used to detect deletions of Y chromosome genes in men with spermatogenic failure. A multiplex polymerase chain reaction amplification system was developed to facilitate rapid screening. Another 24 markers for sequence-tagged sites (STS) were used to ensure the adequacy of gene-based screening. MAIN OUTCOME MEASURE(S): Detection of deletions of Y chromosome genes. RESULT(S): Of 180 patients evaluated, 19 (10.6%) had deletions of one or more genes, including DFFRY, DBY, RBM1, DAZ, CDY1, and BPY2. A second round of STS-based screenings did not show an increase in the deletion rate but more clearly defined the extent of deletion in 14 of the 19 patients. In most patients, deletions detected by gene-based screening were similar to those detected by STS markers. CONCLUSION(S): Gene-based screening with multiplex polymerase chain reaction is a rational alternative for detecting deletions of Y chromosome genes in infertile men.

Adult↗
PubMed2002

Association of a single-nucleotide polymorphism of the deleted-in-azoospermia-like gene with susceptibility to spermatogenic failure.

Single-strand conformation polymorphism analysis of exon-containing genomic DNA segments of the deleted-in-azoospermia-like (DAZL) gene was performed in 160 infertile Taiwanese men presenting with severe oligozoospermia and nonobstructive azoospermia. An A-->G transition at nucleotide 386 in exon 3 was identified. The mutation is located within the RNA-recognition motif (aa 32-117) domain of the DAZL protein and will lead to Thr54-->Ala change (T54A) of DAZL protein. Analysis of cDNA from testicular tissue of infertile carriers showed absence of expression for the T54A allele, implying that the allele carrying T54A polymorphism is hardly, if ever, expressed. The frequencies of T54A allele in patients and the control group were 7.39% and 0.86%, respectively (P = 0.0003). The phenotypes varied significantly in cases with heterozygous T54A polymorphism, ranging from hypospermatogenesis and maturation arrest to Sertoli cell-only syndrome. A combination of DAZ gene deletion and T54A polymorphism did not worsen the phenotype. Our findings provide strong evidence for the role of the autosomal DAZL gene in human spermatogenesis.

Alleles↗
PubMed2002

Referral diagnosis of Prader-Willi syndrome and Angelman syndrome based on methylation-specific polymerase chain reaction.

BACKGROUND AND PURPOSE: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are associated with distinct phenotypes that include mental retardation. Both PWS and AS are caused by loss of function of genes located in chromosome 15q11-q13, an area subject to genomic imprinting. Methylation-specific polymerase chain reaction (M-PCR), based on parent of origin specific DNA methylation at the promoter region of the small nuclear ribonucleoprotein polypeptide N gene (SNRPN), can provide accurate and rapid diagnosis for nearly all PWS patients while it is less accurate for AS patients. We report the development of a referral system for molecular diagnosis of PWS and AS based on M-PCR. METHODS: Pediatric geneticists, psychiatrists, or neurologists were asked to evaluate phenotypes of patients with PWS or AS and complete a questionnaire designed according to the consensus criteria to diagnose these conditions. Molecular analysis based on M-PCR was performed for patients with a score of at least two. RESULTS: A total of 108 patients with suspected PWS and 20 patients with suspected AS were referred for diagnostic testing. PWS was diagnosed in 26 of these patients and AS in two. Among the major diagnostic criteria for PWS, excessive weight gain, developmental delay, and hyperphagia were more prevalent in older patients (> or = 1 yr) than in younger patients. Cerebral hypotonia and developmental delay were significantly more prevalent in older PWS patients than in non-PWS patients. CONCLUSION: M-PCR is a cost-effective method for the diagnosis of PWS and AS. The limitations of current scoring systems and the low cost of M-PCR suggest that routine molecular screening is justified for patients suspected of having PWS.

Adolescent↗
PubMed2002

DiGeorge sequence with hypogammaglobulinemia: a case report.

The most common immunodeficiency in DiGeorge sequence patients is defects in T-cell production due to insufficient thymic tissue. However, because T-lymphocytes are important in regulating antibody responses, DiGeorge sequence is no longer regarded as a pure deficiency of cellular immunity but also a form of variable-combined immunodeficiency. Here we presented a 4-month-old male infant with characteristic facial dysmorphism, thymus dysplasia, tetralogy of Fallot, and documented deletion of chromosome 22q11.2 who had decrease B-lymphocyte numbers and hypogammaglobulinemia. The mitogen responses of T-lymphocytes function were normal with adequate number of CD4+ lymphocytes. This case report highlights the importance of evaluating not only the cellular but also the humoral immune function in patients with DiGeorge sequence.

Agammaglobulinemia↗
PubMedDate not supplied

Potocki-Shaffer syndrome: report of one case.

Potocki-Shaffer syndrome (PSS) results from deletion of proximal short arm of chromosome 11. We present a 14-month-old male baby with cardinal pictures of PSS such as bilateral parietal foraminae, abnormal craniofacial appearance, hypotonia and developmental delay. Cytogenetic study revealed deletion of chromosome 11 from p11.12 to p11.2 in this proband and his mother, but microsatellite marker study showed deletion only in this proband. Despite previous negative chromosome study, positive family history with two similarly affected elder siblings and the finding of bilateral parietal foraminae finally lead to the etiologic diagnosis.

Chromosome Deletion↗