Maurice J. Mahoney

Yale University, New Haven, Connecticut, United States

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Publications (166)1909.69 Total impact

  • No preview · Article · Dec 2011 · Prenatal Diagnosis
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    ABSTRACT: Detection of chromosomal structural abnormalities using conventional cytogenetic methods poses a challenge for prenatal genetic counseling due to unpredictable clinical outcomes and risk of recurrence. Of the 1,726 prenatal cases in a 3-year period, we performed oligonucleotide array comparative genomic hybridization (aCGH) analysis on 11 cases detected with various structural chromosomal abnormalities. In nine cases, genomic aberrations and gene contents involving a 3p distal deletion, a marker chromosome from chromosome 4, a derivative chromosome 5 from a 5p/7q translocation, a de novo distal 6q deletion, a recombinant chromosome 8 comprised of an 8p duplication and an 8q deletion, an extra derivative chromosome 9 from an 8p/9q translocation, mosaicism for chromosome 12q with added material of initially unknown origin, an unbalanced 13q/15q rearrangement, and a distal 18q duplication and deletion were delineated. An absence of pathogenic copy number changes was noted in one case with a de novo 11q/14q translocation and in another with a familial insertion of 21q into a 19q. Genomic characterization of the structural abnormalities aided in the prediction of clinical outcomes. These results demonstrated the value of aCGH analysis in prenatal cases with subtle or complex chromosomal rearrangements. Furthermore, a retrospective analysis of clinical indications of our prenatal cases showed that approximately 20% of them had abnormal ultrasound findings and should be considered as high risk pregnancies for a combined chromosome and aCGH analysis.
    No preview · Article · Jul 2011 · American Journal of Medical Genetics Part A
  • Miriam S. DiMaio · Joyce E. Fox · Maurice J. Mahoney
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    ABSTRACT: How can prenatal testing help your patients? In utero diagnosis has undergone an amazing revolution in recent years. More tests are available; the indications for prenatal diagnosis have expanded - you can now advise your patients about disorders you could not have previously detected. Medical training for obstetricians, medical geneticists, and genetic counselors has not kept pace with these developments. Clinical exposure to common and unusual problems in prenatal diagnosis is limited. Prenatal Diagnosis: Clinical Cases and Challenges, based on the authors' several decades of experiences, fills this gap. Real cases portray diagnostic problems as a route to the underlying biology, the available testing options, and the results that might be obtained. The authors discuss the challenges of management, interpretation, and counseling. Cases used throughout emphasize three types of clinical problems: Chromosomal abnormalities Mendelian disorders Fetal structural abnormalities The decision to enter the world of prenatal diagnosis should be very carefully considered by any prospective mother. Prenatal Diagnosis: Clinical Cases and Challenges will help you discuss the issues in an informed manner with your patients.
    No preview · Article · Jun 2010
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    ABSTRACT: Variable clinical presentations of patients with chromosomally detected deletions in the distal long arm (q) of chromosome 4 have been reported. The lack of molecular characterization of the deletion sizes and deleted genes hinders further genotype-phenotype correlation. Using a validated oligonucleotide array comparative genomic hybridization (oaCGH) analysis, we examined two patients with apparent chromosomal deletions in the distal 4q region. In the first, oaCGH identified a 2.441 megabase (Mb) duplication and a 12.651 Mb deletion at 4q34.1 in a pregnant female who transmitted this aberration to her son. This mother has only learning disabilities while her son had both renal and cardiac anomalies in the newborn period. Unrecognized paternal genetic factors may contribute to the variable expression. The second patient is a 17-year-old female with a history of Pierre Robin sequence, cardiac abnormalities and learning disabilities. She was diagnosed prenatally with a de novo 4q deletion, and oaCGH defined a 16.435 Mb deletion of 4q34.1-4q35.2. Phenotypic comparison and subtractive genomic mapping between these two cases suggested a 4 Mb region possibly harboring a candidate gene for Pierre Robin sequence. Our cases and review of reported cases with genomic findings indicated the presence of familial variants with variable expressivity as well as de novo or inherited pathogenic simple deletion, duplication and complex deletion and duplication in the distal 4q region.
    Full-text · Article · Dec 2009 · American Journal of Medical Genetics Part A
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    ABSTRACT: Pelizaeus-Merzbacher disease is a rare X-linked disorder caused by mutations of the proteolipid protein 1 gene that encodes a structural component of myelin. It is characterized by progressive psychomotor delay, nystagmus, spastic quadriplegia, and cerebellar ataxia. Variable clinical expression was seen in 5 members of a family bearing a novel missense mutation in proteolipid protein 1, c.619T>C. Symptomatic patients included a 6-year-old girl, her younger brother, and their maternal uncle, a 29-year-old college graduate initially diagnosed with cerebral palsy; their brain magnetic resonance imaging studies showed diffuse dysmyelination. The mother had a history of delayed walking, achieved independently by age 3; she and the maternal grandmother were asymptomatic on presentation. Review of clinical information and family history led to consideration of Pelizaeus-Merzbacher disease. Subsequent identification of the causal mutation enabled preimplantation genetic diagnosis and the birth of an unaffected child.
    No preview · Article · Apr 2009 · Journal of child neurology
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    Roger D Klein · Maurice J Mahoney
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    ABSTRACT: In the United States, a longstanding legal rule exists against patenting natural phenomena. The Supreme Court recently had an opportunity to help define the boundaries and clarify the implications of this "natural phenomenon doctrine" in Laboratory Corporation of America v. Metabolite Labs., dismissed as improvidently granted. This article argues that the natural phenomenon doctrine renders both the patent claim at issue in LabCorp, and the patents that directly or indirectly claim biological correlations between genotypes and medical phenotypes, invalid or unenforceable under U.S. patent law.
    Preview · Article · Feb 2008 · The Journal of Law Medicine & Ethics
  • Joe Leigh Simpson · Maurice J. Mahoney
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    ABSTRACT: Definitions and cytological origin of numerical chromosomal abnormalitiesDefinitions and cytological origin of structural chromosomal abnormalitiesSingle gene abnormalities (mendelian inheritance)Molecular basis of the geneMolecular analysis of the gene and its clinical applicabilityPolygenic-multifactorial inheritanceDiagnosis of singlegene disordersScreening for recessive disordersMethods of diagnosisPrenatal diagnosis of specific disordersConclusion Key points
    No preview · Chapter · Jan 2008
  • Roger D Klein · Maurice J Mahoney
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    ABSTRACT: The capacity to diagnose fetal disease or abnormality continues to grow, especially in the genetic definition of the fetus. With this growth have come claims of medical malpractice that have mostly centered on a failure of informed consent. Failure may occur by omission or failed communication of pertinent information to the parents or by alleged error in the interpretation of diagnostic information. The usual claim against a physician or other provider is not that of causing damage or disease in the fetus but of causing a loss of opportunity to prevent conception or live birth of an infant who has an abnormality. Successful suits for "wrongful birth," brought by parents of an abnormal child, are common in many United States jurisdictions, but suits for "wrongful life," brought on behalf of the child, have usually been denied.
    No preview · Article · Jul 2007 · Clinics in Perinatology
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    ABSTRACT: The current revolution in biomedical sciences has raised new hope for early diagnosis, prevention, and treatment of human diseases. Recent advancements in genomics, proteomics, and other basic sciences are currently transforming the medical science, and offer the promise of answering many of the questions related to human diseases, including their early and accurate diagnosis. Profiling of biological fluids (i.e., serum, urine, amniotic fluid, and cerebrospinal fluid) has successfully identified relevant protein biomarkers that potentially can change early diagnosis and treatment of several medical conditions related to human pregnancy. Similarly, proteomics holds the promise to complement genomics to revolutionize screening and prenatal diagnosis of genetic conditions during early pregnancy. This article summarizes current technology and reviews the application of proteomics in diagnosis of genetic disorders during human pregnancy.
    No preview · Article · Apr 2007 · American Journal of Perinatology

  • No preview · Article · Dec 2005 · American Journal of Obstetrics and Gynecology
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    Ray O Bahado-Singh · Utko A Oz · Inanc Mendilcioglu · Maurice J Mahoney
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    ABSTRACT: The genetic sonogram is a composite algorithm combining multiple individual markers to increase Down syndrome risk prediction. Transformation of sonographic information into a standard mathematical format represented an early challenge that has now been surmounted. Using increasingly sophisticated mathematical techniques, individual patient risk can be estimated. High diagnostic accuracy comparable to standard mid-trimester serum algorithms has been reported. Most recently, a few studies have reported the ability to combine serum and biochemical markers to achieve diagnostic accuracy comparable to first-trimester screen. Even fewer studies have reported combinations of ultrasound and maternal urine markers. While it is clear that consistently high sensitivity and specificity for Down syndrome can be achieved, almost all the studies are based on high-risk groups. Studies in low-risk populations have suffered from lack of standardization. The relevance of genetic sonogram in a low-risk population thus remains to be proven. The most significant challenge, however, remains the development of uniform and reproducible sonographic and measurement standards. This is likely to be the most important factor in optimizing the accuracy of the mid-trimester genetic sonogram.
    Preview · Article · Sep 2005 · Seminars in Perinatology
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    ABSTRACT: To document our experience with fragile X carrier screening. In this study, 29,103 women with no known or suspected family history of fragile X syndrome were offered fragile X carrier screening during their prenatal genetic counseling visit. Screening acceptance was analyzed by referral indication, carrier frequencies documented, and prenatal outcome data presented. Overall, 7.9% accepted carrier screening. The premutation frequency was 1 in 382, and the intermediate allele frequency was 1 in 143. Fragile X screening is a desirable option for some women seeking prenatal genetic counseling and should be made available to this population.
    Preview · Article · May 2005 · Genetics in Medicine
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    ABSTRACT: Objective: We sought to evaluate the association between first trimester nuchal translucency measurement and the risk for major congenital heart defect in chromosomally normal fetuses. Study design: First trimester (10 weeks 4 days of gestation to 13 weeks 6 days of gestation) nuchal translucency was obtained in a large prospective multicenter National Institute of Child Health and Human Development study for Down syndrome prediction. The study, which was conducted between May 1998 and December 2000, was restricted to singleton pregnancies. Gestational age was determined by crown rump length measurements. Perinatal outcomes were determined and included the frequency of major congenital heart defect, which was defined as those cases that potentially could require surgery, intensive medical therapy, or prolonged followup time. Logistic regression analysis was used to determine whether nuchal translucency was a significant predictor of congenital heart defect.
    No preview · Article · May 2005 · American Journal of Obstetrics and Gynecology
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    ABSTRACT: To evaluate the potential relationship between placental disruption in weeks 13 and 14 and the subsequent development of gestational hypertension or preeclampsia. Using subjects recruited during a randomized trial funded by the National Institute of Child Health and Human Development, which compared early amniocentesis and late transabdominal chorionic villus sampling (CVS) in weeks 13 and 14, rates of gestational hypertension and preeclampsia were compared between cases with varying degrees of placental disruption. A total of 3,698 of 3,775 randomized subjects had cytogenetically normal pregnancies and were analyzed. A significantly higher rate of hypertension/preeclampsia was observed in the late CVS group (5.4%, n = 1,878) compared with the early amniocentesis cohort (3.5%, n = 1,820; P = .005). This difference persisted after controlling for maternal age, body mass index, parity, previous preterm delivery, smoking, and fetal gender. Early amniocentesis cases were further stratified on the basis of whether the placenta had been penetrated (n = 460) or not (n = 1,360). Risk of hypertensive complications was lowest if the placenta was not traversed (3.4%), greater with placental penetration (3.9%), and highest when the placenta was directly sampled during CVS (5.4%, P = .02). We hypothesize that focal disruption of the placenta at 13-14 weeks may increase the risk of hypertension/preeclampsia. These findings provide support for the theory that disturbances in early placentation lead subsequently to maternal hypertension.
    No preview · Article · Apr 2005 · Obstetrics and Gynecology

  • No preview · Article · Apr 2005 · Ugeskrift for laeger
  • Ray O. Bahado-singh · Maurice J. Mahoney · Julia Zachary · Ronald J. Wapner

    No preview · Article · Dec 2004 · American Journal of Obstetrics and Gynecology
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    ABSTRACT: To evaluate the performance and use of second-trimester multiple-marker maternal serum screening for trisomy 21 by women who had previously undergone first-trimester combined screening (nuchal translucency, pregnancy-associated plasma protein A, and free beta-hCG), with disclosure of risk estimates. In a multicenter, first-trimester screening study sponsored by the National Institute of Child Health and Human Development, multiple-marker maternal serum screening with alpha-fetoprotein, unconjugated estriol, and total hCG was performed in 4,145 (7 with trisomy 21) of 7,392 (9 with trisomy 21) women who were first-trimester screen-negative and 180 (7 with trisomy 21) of 813 (52 with trisomy 21) who were first-trimester screen-positive. Second-trimester risks were calculated using multiples of the median and a standardized risk algorithm with a cutoff risk of 1:270. Among the first-trimester screen-negative cohort, 6 of 7 (86%) trisomy 21 cases were detected by second-trimester multiple-marker maternal serum screening with a false-positive rate of 8.9%. Among the first-trimester screen-positive cohort, all 7 trisomy 21 cases were also detected in the second trimester, albeit with a 38.7% false-positive rate. Our data demonstrate that a sequential screening program that provides patients with first-trimester results and offers the option for early invasive testing or additional serum screening in the second trimester can detect 98% of trisomy 21-affected pregnancies. However, such an approach will result in 17% of patients being considered at risk and, hence, potentially having an invasive test. II-2
    No preview · Article · Nov 2004 · Obstetrics and Gynecology
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    ABSTRACT: The purpose of this study was to determine the association between first-trimester trisomy 21 screening markers (free human chorionic gonadotropin-beta [hCG], pregnancy-associated plasma protein A [PAPP-A], and nuchal translucency) and adverse pregnancy outcome. This was a cohort study of 8012 patients enrolled in a National Institute of Child Health and Human Development-sponsored study of first-trimester trisomy 21 and 18 screening. Trisomy 21 and 18 risk results and individual marker levels in unaffected pregnancies and pregnancies with adverse outcomes were evaluated. PAPP-A <1st percentile (OR 5.4, 95% CI 2.8-10.3) and PAPP-A <5th percentile (OR 2.7, 95% CI 1.9-3.9) and free beta-hCG <1st percentile (OR 2.7, 95% CI 1.3-5.9) were associated with increased risk of intrauterine growth restriction (IUGR) with positive predictive values of 24.1%, 14.1%, and 14.3%, respectively. PAPP-A <5th percentile (OR 2.3 95% CI 1.1-4.7) and nuchal translucency >99th percentile (OR 3.5, 95% CI 1.1-11.3) were associated with increased risk of preterm delivery before 34 weeks. Increased risk at screening for trisomy 21 and 18 identified 16 of the 29 other chromosomal abnormalities (55%). Low free beta-hCG, low PAPP-A, and increased nuchal translucency were all associated with an increased rate of fetal abnormality. Extreme values of first-trimester free beta-hCG, PAPP-A, and nuchal translucency are all associated with adverse outcomes. The especially high predictive value for IUGR of PAPP-A levels below the 1st percentile suggests that patients within this group may benefit from increased surveillance for this condition.
    No preview · Article · Nov 2004 · American Journal of Obstetrics and Gynecology
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    ABSTRACT: To estimate the likelihood of clinical early and late pregnancy loss as a function of first-trimester maternal serum analytes and fetal nuchal translucency measurements. Study subjects were recruited for a National Institute of Child Health and Human Development-sponsored multicenter cohort study initially designed to study the detection of Down syndrome during the first trimester of pregnancy. The cohort consisted of women who had a live fetus between 10 and 14 weeks of gestation and had no significant vaginal bleeding. Women with prior fetal trisomy (T21/18) and those with structural or chromosomal abnormalities in the index pregnancy were excluded. First-trimester screening consisted of pregnancy-associated plasma protein A (PAPP-A), free beta-hCG, and nuchal translucency. Pregnancy loss rates in women with various levels of PAPP-A, free beta-hCG, or nuchal translucency (less than 1st, less than 5th, more than 95th, and more than 99th percentile) were compared with losses in women with normal values (5th to 95th percentile). The mean gestational age at screening of 7,932 women meeting study criteria was 12.1 weeks. Loss rates were only 0.36% at less than 20 weeks after normal free beta-hCG, PAPP-A, and nuchal translucency. Conversely, low levels of PAPP-A and free beta-hCG as well as increased nuchal translucency were individually associated with increased early loss. These associations persisted after controlling for maternal age and race using logistic regression analysis. Normal values of PAPP-A, free beta-hCG, and nuchal translucency are associated with a very low risk of pregnancy loss at less than 20 weeks.
    No preview · Article · Aug 2004 · Obstetrics and Gynecology
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    ABSTRACT: To assess, in a randomized trial, the safety and accuracy of amniocentesis and transabdominal chorionic villus sampling (CVS) performed at 11-14 weeks of gestation, given that this time frame is increasingly relevant to early trisomy screening. We compared amniocentesis with CVS from 77 to 104 days of gestation in a randomized trial in a predominantly advanced maternal age population. Before randomization, the feasibility of both procedures was confirmed by ultrasonography, and experienced operators performed sampling under ultrasound guidance; conventional cytogenetic analysis was employed. The primary outcome measure was a composite of fetal loss plus preterm delivery before 28 weeks of gestation in cytogenetically normal pregnancies. We randomized 3,775 women into 2 groups (1,914 to CVS; 1,861 to amniocentesis), which were comparable at baseline. More than 99.6% had the assigned procedure, and 99.9% were followed through delivery. In contrast to previous thinking, in the cytogenetically normal cohort (n = 3,698), no difference in primary study outcome was observed: 2.1% (95% confidence interval 1.5, 2.8) for CVS and 2.3% (95% confidence interval, 1.7, 3.1) for amniocentesis. However, spontaneous losses before 20 weeks and procedure-related, indicated terminations combined were increased in the amniocentesis group (P =.07, relative risk 1.74). We found a 4-fold increase in the rate of talipes equinovarus after amniocentesis (P =.02) overall and in week 13 (P =.03, relative risk = 4.65), but data were insufficient to determine this risk in week 14. Amniocentesis at 13 weeks carries a significantly increased risk of talipes equinovarus compared with CVS and also suggests an increase in early, unintended pregnancy loss. I
    Full-text · Article · Jul 2004 · Obstetrics and Gynecology

Publication Stats

6k Citations
1,909.69 Total Impact Points


  • 1974-2011
    • Yale University
      • • Department of Genetics
      • • School of Medicine
      • • Department of Pediatrics
      New Haven, Connecticut, United States
  • 1970-2011
    • Yale-New Haven Hospital
      • Department of Pathology
      New Haven, Connecticut, United States
  • 2004
    • Drexel University
      Filadelfia, Pennsylvania, United States
    • Drexel University College of Medicine
      • Department of Obstetrics and Gynecology
      Filadelfia, Pennsylvania, United States
  • 1983-1993
    • Wayne State University
      • Department of Obstetrics and Gynecology
      Detroit, Michigan, United States
  • 1992
    • Baylor College of Medicine
      Houston, Texas, United States
  • 1988-1992
    • University of New Haven
      New Haven, Connecticut, United States
  • 1984-1992
    • Icahn School of Medicine at Mount Sinai
      • Department of Obstetrics, Gynecology, and Reproductive Science
      Manhattan, New York, United States
  • 1990
    • Bridgeport Hospital
      Bridgeport, Connecticut, United States
  • 1989
    • Brown University
      Providence, Rhode Island, United States
  • 1985
    • Mount Sinai Medical Center
      New York, New York, United States