W. Hogge - Academia.edu (original) (raw)

Papers by W. Hogge

American Journal of Medical Genetics, 1985

Journal of Assisted Reproduction and Genetics, 2013

Purpose Immune response to infections has been associated with recurrent pregnancy loss (RPL). Lo... more Purpose Immune response to infections has been associated with recurrent pregnancy loss (RPL). Low plasma mannose binding lectin (MBL) levels, an innate immunity factor in infections, has been related to RPL. In this study, we tested the hypothesis that MBL genotypes that are known to cause reduced plasma MBL levels are significantly more frequent among women experiencing unexplained RPL. Methods This study included 219 Caucasian women diagnosed with unexplained RPL and 236 control women. All participants were genotyped for two promoter (−550 C > G and −221 G > C) and three missense (R52C, G54D and G57E) mutations in exon 1. These mutations are known to be associated with variations in plasma MBL levels. Genotype frequencies were estimated by gene counting and were compared to the expectation of Hardy-Weinberg equilibrium by chi-squared (X 2) analysis and Fisher's exact test. Allele and genotype frequencies were compared in cases and controls using X 2 contingency table analysis. Results There was no difference in demographics between cases and controls. The number of miscarriages in the participants with RPL ranged from 2 to 10 spontaneous abortions (SAB's) per participant. Populations genotyped were in Hardy-Weinberg equilibrium. There was no association between a history of RPL and multi-SNP genotypes at the MBL locus. In unexplained RPL, the number of SAB's and live birth rates were unaffected by MBL genotype. There was no association between MBL genotype and the risk of unexplained RPL. The occurrence of live birth was not associated with MBL genotype. Conclusion Genotypes known to cause low MBL plasma levels are not associated with an increased risk of unexplained RPL.

Prenatal Diagnosis, 2014

Background/Objective: The non-invasive prenatal detection of fetal microdeletions becomes increas... more Background/Objective: The non-invasive prenatal detection of fetal microdeletions becomes increasingly challenging as the size of the mutation decreases, with current practical lower limits in the range of a few Mb. Our goals were to explore the lower limits of microdeletion size detection via NIPT using MINK and introduce/evaluate a novel statistical approach we recently developed called the GC Content Random Effect Model (GCREM). Methods: Maternal plasma was obtained from a pregnancy affected by a 4.2Mb fetal microdeletion and three normal controls. Plasma DNA was subjected to capture of an 8Mb sequence spanning the breakpoint region and sequenced. Data were analyzed with our published method, Minimally Invasive Karyotyping (MINK) and a new method called GCREM. Results: The 8Mb capture segment was divided into either 38 or 76 non-overlapping regions of 200Kb and 100Kb respectively. At 200Kb resolution, using GCREM (but not MINK) we obtained significant adjusted p values for all 20 regions overlapping the deleted sequence, and nonsignificant p values for all 18 reference regions. At 100Kb resolution, GCREM identified significant adjusted p values for all but one 100Kb region located inside the deleted region. Conclusion: Targeted sequencing and GCREM analysis may enable cost effective detection of fetal microdeletions and microduplications at high resolution.

The American Journal of Human Genetics, 1999

Mutations of UFD1L Are Not Responsible for the Majority of Cases of DiGeorge Syndrome/ Velocardio... more Mutations of UFD1L Are Not Responsible for the Majority of Cases of DiGeorge Syndrome/ Velocardiofacial Syndrome without Deletions within Chromosome 22q11 To the Editor: Deletions of chromosome 22q11 are associated with a wide spectrum of congenital malformation, encompassed by the acronym "CATCH22" (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, and hypocalcemia on chromosome 22), including velocardiofacial syndrome (VCFS; MIM 192430), DiGeorge syndrome (DGS; MIM 188400), and conotruncal-anomaly face (Emanuel et al. 1998). The major anomalies include outflow-tract congenital heart defects, hypoplasia of the parathyroids and thymus, craniofacial dysmorphism, and learning/behavioral problems (Ryan et al. 1997). Many of these are thought to be due to a defective neural-crest contribution during development. The DiGeorge chromosomal region (DGCR) is entirely cloned (Carlson et al. 1997) and sequenced, and several genes have been reported mapping to the region. Mutation screens of genes mapping to the proximal end of this region, termed the "minimal DiGeorge chromosomal region" (MDGCR; Gong et al. 1996), have been negative (Wadey et al. 1995; Gong et al. 1997; Gottlieb et al. 1997; Lindsay et al. 1998). Attention therefore has turned to the regions adjacent and distal to the MDGCR. Recently, the gene UFD1L was proposed as the major gene haploinsufficient in this group of syndromes (Yamagishi et al. 1999). UFD1L is downstream of dHAND, a gene known to be involved in control of the development of structures affected in DGS, and Ufd1l is expressed in the branchial arches, frontonasal mass, and outflow tract. In addition, a single patient has been reported with a de novo deletion affecting UFD1L and the neighboring gene, CDC45L2 (Yamagishi et al. 1999). CDC45 is required for initiation of DNA replication in yeast, and CDC45 mutants are nonviable. However, CDC45L2 expression is not altered in d-HAND Ϫ/Ϫ embryos. On the basis of these findings, Yamagishi and colleagues concluded that UFD1L hap-conditions can be obtained at the e-mail addresses that follow:

The New England …, 2003

Ronald Wapner, MD, Elizabeth Thom, Ph.D., Joe Leigh Simpson, MD, Eugene Pergament, MD, Ph.D., Ric... more Ronald Wapner, MD, Elizabeth Thom, Ph.D., Joe Leigh Simpson, MD, Eugene Pergament, MD, Ph.D., Richard Silver, MD, Karen Filkins, MD, Lawrence Platt, MD, Maurice Mahoney, MD, Anthony Johnson, DO, W. Allen Hogge, MD, R. Douglas Wilson, MD, Patrick Mohide, ...

Schizophrenia Research, 1995

American Journal of Obstetrics and Gynecology, 2001

Unexplained recurrent spontaneous abortion is a common women&amp;#39;s health problem tha... more Unexplained recurrent spontaneous abortion is a common women&amp;#39;s health problem that affects approximately 1 of every 200 women who wish to have children. It has long been assumed that a large proportion of recurrent spontaneous abortion results from genetic problems, but no causative genes have been identified to date. Here, we tested the hypothesis that a subset of women with recurrent spontaneous abortion are carriers of X-linked recessive disorders that result in the loss of male pregnancies. X chromosome inactivation patterns, an assay used to detect women who are likely to be carriers of X-linked recessive cell-lethal traits, were compared between 105 female patients with idiopathic recurrent pregnancy loss and 101 women (control subjects) with a single successful pregnancy and no history of pregnancy loss. Inheritance patterns and gender of offspring were studied in relevant subsets of participants. Female patients showed a highly statistically significant increase in the frequency of skewed X chromosome inactivation (90%; P &amp;lt; .0005). Female patients with highly skewed X chromosome inactivation showed a significant decrease in male children. Four of 6 families that were studied showed maternal inheritance of the skewed inactivation trait. We found the 14% of women with unexplained recurrent pregnancy loss show highly skewed X inactivation, which suggests that they are carriers of X-linked recessive lethal traits. Furthermore, the observed gender bias among women with highly skewed X inactivation suggests selective loss of male conceptions, which is consistent with an X chromosome-linked genetic defect that leads to cell death or growth disadvantage. Identification of such female carriers is important for the reproductive counseling and treatment of these women.

American Journal of Obstetrics and Gynecology, 2003

OBJECTIVE: The objective of this study was to assess the clinical use of routinely karyotyping sp... more OBJECTIVE: The objective of this study was to assess the clinical use of routinely karyotyping spontaneous abortion material. STUDY DESIGN: We retrospectively reviewed the records of the Pittsburgh Cytogenetics Laboratory from January 1, 1998, to December 31, 2001, for all tissues from spontaneous losses at 20 weeks' gestation or less for which complete medical records were available. RESULTS: There were 517 submitted samples of which 28 (5.4%) failed to grow in culture. Overall, 55.8% of samples were abnormal; 52.3% of normal results were male. In samples from pregnancies at 13 weeks or less the rate of abnormality was 69.1%. When analyzed by maternal age, the rate of abnormality for first-trimester losses was 57.2% in women younger than 35 years, and 82.3% in those 35 years or older. There was no difference in the rate of abnormality when comparing first loss with two or more losses, first pregnancy with two or more pregnancies, or the presence or absence of at least one live birth. CONCLUSION: Chromosome abnormalities are the cause for pregnancy loss in 50% to 80% of cases, depending on maternal age and gestational age at time of the loss. Karyotyping of spontaneous losses in the first trimester beginning with the patient's second loss provides clinically important etiologic information and decreases the number of evaluations necessary for recurrent pregnancy loss. (Am J Obstet Gynecol 2003;189:397-402.)

American Journal of Medical Genetics, 2002

We report three cases of tetrasomy 9p, two of which were confirmed prenatally. All three had char... more We report three cases of tetrasomy 9p, two of which were confirmed prenatally. All three had characteristic findings on ultrasound and at birth. We also present a review of the literature, which suggests that a recognizable phenotype for this condition is emerging. Common findings on prenatal ultrasound include intrauterine growth restriction, ventriculomegaly, cleft lip or palate, and renal anomalies. These findings can provide a clue toward the prenatal diagnosis of this condition. There is also a clearly recognizable phenotype at birth. Facial characteristics include hypertelorism, broad nasal bridge/ bulbous or beaked nose, cleft lip/palate, ear anomalies, and micrognathia. The exact extent of the isochromosome does not seem to predict severity, but mosaic cases are less severe, or at least have a greater probability of survival. ß

American Journal of Medical Genetics, 1996

Using a case-control design, an association of schizophrenia with the dopamine D3 receptor gene (... more Using a case-control design, an association of schizophrenia with the dopamine D3 receptor gene (D3RG) locus was investigated. Initial analysis of pooled results from published studies revealed a significant excess of individuals homozygous for either allele among the patients. The association was next tested in two cohorts ascertained independently at Pittsburgh, Pennsylvania and at Houston, Texas. The Pittsburgh sample was comprised of patients with schizophrenia (DSM-III-R) (n = 130). The controls belonged to two groups: adults screened for the absence of substance abuse or major psychiatric illness (n = 128), and neonates (n = 160). Multivariate analysis suggested an association with allele 1 of the biallelic D3RG polymorphism in comparison with the adult, but not the neonatal, controls. The association was most marked among Caucasian patients with a family history of schizophrenia (odds ratio 13.69, confidence intervals 1.80, 104.30). Survival analysis suggested an earlier age of onset among male patients homozygous for allele 2. The Houston cohort included Caucasian patients with schizophrenia or schizoaffective disorder (DSM-III-R criteria, n = 50), and normal controls matched for gender (n = 51). In this group, no significant associations were noted among all the patients or among subgroups of patients based on family history or age of onset. Possible reasons for the discordant results are discussed.

Placenta, 2009

Background: Preeclampsia is a pregnancy-specific disorder that remains a leading cause of materna... more Background: Preeclampsia is a pregnancy-specific disorder that remains a leading cause of maternal, fetal and neonatal morbidity and mortality, and is associated with risk for future cardiovascular disease. There are no reliable predictors, specific preventative measures or treatments other than delivery. A widely held view is that the antecedents of preeclampsia lie with impaired placentation in early pregnancy. Accordingly, we hypothesized dysregulation of global gene expression in first trimester placentas of women who later manifested preeclampsia.