Janice G. Edwards

PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects.

The human eye malformation aniridia results from haploinsufficiency of PAX6, a paired box DNA–binding protein. To study this dosage effect, we characterized two PAX6 mutations in a family segregating aniridia and a milder syndrome consisting of congenital cataracts and late onset corneal dystrophy. The nonsense mutations, at codons 103 and 353, truncate PAX6 within the N–terminal paired and C–terminal PST domains, respectively. The wild–type PST domain activates transcription autonomously and the mutant form has partial activity. A compound heterozygote had severe craniofacial and central nervous system defects and no eyes. The pattern of malformations is similar to that in homozygous Sey mice and suggests a critical role for PAX6 in controlling the migration and differentiation of specific neuronal progenitor cells in the brain.

Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine.

The Perinatal Quality Foundation and the American College of Medical Genetics and Genomics, in association with the American College of Obstetricians and Gynecologists, the Society for Maternal-Fetal Medicine, and the National Society of Genetic Counselors, have collaborated to provide education for clinicians and laboratories regarding the use of expanded genetic carrier screening in reproductive medicine. This statement does not replace current screening guidelines, which are published by individual organizations to direct the practice of their constituents. As organizations develop practice guidelines for expanded carrier screening, further direction is likely. The current statement demonstrates an approach for health care providers and laboratories who wish to or who are currently offering expanded carrier screening to their patients.

Prenatal diagnosis of Down syndrome: a systematic review of termination rates (1995–2011)

The objective of this study was to review the published literature on pregnancy termination following a prenatal diagnosis of Down syndrome in the United States.

Ethical issues in genetic counseling: A comparison of M.S. counselor and medical geneticist perspectives

New technologies available in the field of medical genetics have increased the importance of responsible ethical decision-making among genetic counselors. A 1985 national survey of M.D. and Ph.D. genetic counselors assessed ethical attitudes using case scenarios designed to simulate dilemmas faced in genetic counseling (Wertz and Fletcher, 1988b). The current study focuses on attitudes of M.S. genetic counselors using similar scenarios, allowing for effective comparisons. M.S. counselors were more willing than M.D. and Ph.D. counselors to maintain patient confidentiality when screening for Huntingtons Disease and occupational diseases, and a greater number would agree to counsel patients pursuing prenatal testing for sex selection. A majority of M.S. counselors would disclose an XY karyotype to a phenotypically female patient. M.S. counselors reasoned that respect for patient autonomy and patient confidentiality justified their decisions in many cases. The importance of these principles is discussed and questioned.

Fragile X Syndrome in a Population of Autistic Children

Fragile X syndrome, a recently described form of X-linked mental retardation, has been reported to be associated with infantile autism. In chromosomal analysis of 40 children who met DSM-III criteria for infantile autism, a large number of possible autosomal fragile sites were noted, but only one child was positive for fragile X. The authors concluded that the association of fragile X syndrome and infantile autism may be less frequent than previously thought.

Paternal Paracentric Inversion of Chromosome 2: A Possible Association with Recurrent Pregnancy Loss and Infertility

As follow-up, the couple was seen for genetic counSome 15% of clinically recognized pregnancies seling. While it is understood that paracentric inverbetween 4–20 weeks undergo spontaneous abortion sions can cause pregnancy loss, it generally is not (1). True loss, however may be closer to 50%, since expected to result in multiple consecutive losses. To many early pregnancies go clinically unrecognized (2). investigate the proportion of sperm that had undergone Most early losses are associated with chromosomal recombination on chromosome 2, molecular cytogeabnormalities in sperm or egg and result in arrested netic analysis of sperm was performed. Using fluoresembryonic development and/or failed implantation (2). cently labeled DNA probes unique to the alpha satellite Recurrent abortion is defined as three or more conregion of chromosome 2, 496 spermatozoa were scored secutive pregnancy losses (3). This occurs in 0.5–1% for chromosome 2 signals. The expected pattern for of pregnant women (3). Multiple etiologies for recurnormal spermatozoa would be a single signal for chrorent abortion have been discussed including genetic mosome 2. Recombination of a paracentric inversion abnormalities, immunologic factors, luteal-phase should lead to spermatozoa with either two (dicentric) defect, uterine anomalies, infection, and metabolic and or zero (acentric) signals. A second DNA probe was hormonal disorders (4). Therefore, standard evaluation tested as an internal control (chromosome 17 alpha is reasonable, realizing that up to 50% of couples will satellite). Results of the sperm analysis showed that have no identifiable cause (4). among spermatozoa with a single alpha-satellite chroTwo brothers with reproductive failure are premosome 17 signal, two cells showed no signals for sented. Both have a paracentric inversion on the long chromosome 2, 492 cells showed a single signal for arm of chromosome 2. Only three other such familial chromosome 2, and two cells showed two signals for cases have been documented in the world literature. chromosome 2. Thus, 4 of 496 cells, or 0.8%, yielded This is the first case involving males with reproduca pattern consistent with unbalanced recombinants of tive failure. the inversion on chromosome 2.

Single-center comparison of results of 1000 prenatal diagnoses with chorionic villus sampling and 1000 diagnoses with amniocentesis

Large multicenter studies have confirmed the safety and accuracy of chorionic villus sampling as a prenatal genetic diagnostic procedure, but there have been few single-center evaluations. We report our experience with 1000 consecutive chorionic villus sampling procedures compared with 1000 consecutive amniocentesis procedures during the same period. The procedures were performed by the same genetic counselors, sonographers, obstetricians, and laboratory personnel. Indications for referral, demographic characteristics of patients, numbers of attempts per patient, fetal loss rates, laboratory results, and evaluation of accuracy are included. Analysis of all data suggests that chorionic villus sampling is a safe and accurate alternative to amniocentesis in our community-based teaching hospital.

Pushing Through the Door.

Thanksgiving weekend started off rather roughly. Wednesday afternoon, my chairman came by my office to let me know that in the midst of a reorganization, the School of Medicine no longer considered me a faculty member. They would soon put me in a staff position, stripping me of my clinical associate professor title. I had held a faculty title for several years, first as an instructor, then moving up the ranks to assistant and associate professor. The problem, they said, lay in an administrative quirk: I had been a community hospital employee holding an essentially honorary faculty title. After 15 years in this situation, the genetic counselors were among a group of hospital employees being transferred into the university system. Some 200 hospital employees were transferred, and human resources had to identify the appropriate university slot for each. Not surprisingly, the genetic counselors were the last to be reclassified, as they did not quite know how to pigeon hole us. We were asked whether we preferred to be classified as staff employees or as faculty. Staff positions were considered more secure since the faculty served on 1-year contracts and could be dismissed at anytime. I knew in my heart that mine was more an academic position, while my coworkers requested staff classification. Needless to say, my chairman’s news left me with a broken spirit. Yet I knew that if I accepted a staff position, I would not be true to myself and would limit my future professional growth. Thanksgiving weekend was filled with cooking, eating, and relatives, which kept me occupied and allowed me to process and plan for Monday morning. I remember telling my mother-in-law, “I will find a way to turn around my dejected feelings and put a positive focus in my response.” That response formed itself into a letter to my chair restating my request to be classified as full faculty and citing the many ways in which my work reflected

The Transnational Alliance for Genetic Counseling: Promoting International Communication and Collaboration

The Transnational Alliance for Genetic Counseling seeks to promote communication and collaboration among genetic counselor educators, internationally. Connecting and building global relationships among colleagues also promotes the development of the genetic counseling profession. Genetic counselors everywhere can achieve deeper understanding of their work by seeking international perspectives.

Prenatal Detection of 10q22q23 Duplications: Dilemmas in Phenotype Prediction

The phenotype for 10q22q23 duplication is diverse, ranging from intellectual disability and dysmorphism to normal development. Interpreting the clinical significance of the duplication identified in this region is difficult, especially in the prenatal setting. This study aimed to characterize the prenatal findings associated with this submicroscopic imbalance and discuss the dilemmas in predicting the phenotype of 10q22q23 duplications.