The relationship between performance on the medical genetics and genomics in-training and certifying examinations.

Purpose: The American Board of Medical Genetics and Genomics (ABMGG) certifying examinations (CEs) are designed to assess relevant basic knowledge, clinical knowledge, and diagnostic skills of board-eligible candidates in primary specialty areas. The ABMGG in-training examinations (ITEs) provide formative feedback regarding knowledge and learning over time and assess readiness to attempt board certification. This study addresses the validity of the ABMGG ITE by evaluating its relationship with performance on CE utilizing established psychometric approaches.

Training the next generation of genomic medicine providers: trends in medical education and national assessment.

Purpose: To assess the utilization of genetics on the United States Medical Licensing Examination (USMLE®).

Methods: A team of clinical genetics educators performed an analysis of the representation of genetics content on a robust sample of recent Step 1, Step 2 Clinical Knowledge (CK), and Step 3 examination forms. The content of each question was mapped to curriculum recommendations from the peer reviewed Association of Professors of Human and Medical Genetics white paper, Medical School Core Curriculum in Genetics, and the USMLE Content Outline.

Targeted exome analysis identifies the genetic basis of disease in over 50% of patients with a wide range of ataxia-related phenotypes.

Purpose: To examine the impact of a targeted exome approach for the molecular diagnosis of patients nationwide with a wide range of ataxia-related phenotypes.

Methods: One hundred and seventy patients with ataxia of unknown etiology referred from clinics throughout the United States and Canada were studied using a targeted exome approach. Patients ranged in age from 2 to 88 years.

The natural history of phytosterolemia: Observations on its homeostasis.

Background And Aims: Phytosterolemia is a rare genetic disease caused by mutation of the ABCG5/8 gene. Our aim was to elucidate the natural history and homeostasis of phytosterolemia.

Methods: We analyzed a Hutterite kindred consisting of 21 homozygotes with phytosterolemia assembled over a period of two decades, all of whom carried the ABCG8 S107X mutation and were treated with ezetimibe.

BATTEN DISEASE CAUSED BY A NOVEL MUTATION IN THE PPT1 GENE.

Purpose: To report a case of Batten disease due to a previously unreported mutation in PPT1.

Methods: A 9-year-old girl presented with classic clinical findings of Batten Disease.

Results: Genetic testing for the mutations in the most common Batten disease gene, CLN3, was negative.

A Review of Fanconi Anemia for the Practicing Pediatrician.

Early recognition of a patient who might have Fancomi anemia by the general pediatrician and referral to a tertiary care center with a dedicated cancer risk program is critical for early diagnosis. Genetic testing and close multidisciplinary surveillance is required for patients with this syndrome and their families because of its multisystem involvement and propensity for early-onset bone marrow failure and leukemic transformation. This article reviews the clinical symptoms and signs, radiologic findings, and screening guidelines of FA for the general pediatrician.

Disclosure of genetic research results to members of a founder population.

There is currently extensive discussion and debate in the literature on how, when, and to whom genetic research results should be returned (see Genetics in Medicine, April 2012 issue). Here, we describe our experience in disclosing genetic information on Mendelian disorders discovered during the course of our research in the Hutterites. We first assessed attitudes toward the disclosure of carrier results, which revealed that many individuals wanted carrier information and that many intended to use the information in family planning.

Professional medical education and genomics.

Genomic medicine is a relatively new concept that involves using individual patients' genomic results in their clinical care. Genetic technology has advanced swiftly over the past decade, and most providers have been left behind without an understanding of this complex field. To realize its full potential, genomic medicine must be both understood and accepted by the greater medical community.

Internet resources in medical genetics.

This unit presents an overview of the most commonly used Web-based information resources for clinicians seeking to apply molecular or array-based genetic testing to patient care, learn more about newborn screening, or understand the molecular basis of inherited diseases. It is also for consumers seeking advocacy or scientific/management information, and for genetics professional societies.

Reciprocal deletion and duplication at 2q23.1 indicates a role for MBD5 in autism spectrum disorder.

Copy number variations associated with abnormal gene dosage have an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID) and autism. We hypothesize that the chromosome 2q23.1 region encompassing MBD5 is a dosage-dependent region, wherein deletion or duplication results in altered gene dosage.

RUNX2 quadruplication: additional evidence toward a new form of syndromic craniosynostosis.

The RUNX2 transcription factor regulates osteoblast differentiation. Its absence, as with cleidocranial dysplasia, results in deficient bone formation. However, its excess seems to follow a dose response of over ossification.

Expanding newborn screening for lysosomal disorders: opportunities and challenges.

Newborn screening (NBS), since its implementation in the 1960s, has traditionally been successful in reducing mortality and disability in children with a range of different conditions. Lysosomal storage disorders (LSD) are a heterogeneous group of inherited metabolic diseases that result from lysosomal dysfunction. Based on available treatment and suitable screening methods, the LSDs that are considered for NBS generally include Fabry, Gaucher, Krabbe, MPSI, MPSII, MPSV, Metachromatic leukodystrophy, Niemann-Pick, and Pompe.

Evidence of a mechanism for isodicentric chromosome Y formation in a 45,X/46,X,idic(Y)(p11.31)/46,X,del(Y)(p11.31) mosaic karyotype.

Abnormalities involving sex chromosomes account for approximately 0.5% of live births. The phenotypes of individuals with mosaic cell lines having structural aberrations of the X and Y chromosomes are variable and hard to accurately predict.

Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies.

Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA.

SMC1A expression and mechanism of pathogenicity in probands with X-Linked Cornelia de Lange syndrome.

Cornelia de Lange Syndrome (CdLS) is a dominantly inherited heterogeneous genetic disorder with multisystem abnormalities. Sixty percent of probands with CdLS have heterozygous mutations in the Nipped-B-like (NIPBL) gene, 5% have mutations in the SMC1A gene, and one proband was found to have a mutation in the SMC3 gene. Cohesin is a multisubunit complex consisting of a SMC1A and SMC3 heterodimer and two non-SMC subunits.

Internet resources in medical genetics.

This unit presents an overview of the most commonly used Web-based information resources for clinicians seeking to apply molecular or array-based genetic testing to patient care, obtain information on metabolic disease testing, learn more about newborn screening, or understand the molecular basis of inherited diseases, as well as for consumers seeking advocacy or scientific/management information, and also for genetics professional societies.

Paternal deletion 6q24.3: a new congenital anomaly syndrome associated with intrauterine growth failure, early developmental delay and characteristic facial appearance.

Deletions of the long arm of chromosome 6 are relatively uncommon and to date minimal genotype-phenotype correlations have been observed. We report on three unrelated patients with de novo paternal interstitial deletions of 6q24.3.

Mosaicism del(22)(q11.2q11.2)/dup(22)(q11.2q11.2) in a patient with features of 22q11.2 deletion syndrome.

The chromosome 22q11 region is prone to rearrangements, including deletions and duplications, due to the presence of multiple low copy repeats (LCRs). DiGeorge/velo-cardio-facial syndrome is the most common microdeletion syndrome with more than 90% of patients having a common 3-Mb deletion of 22q11.2 secondary to non-homologous recombination of flanking LCRs.

Integration of internet-based genetic databases into the medical school pre-clinical and clinical curriculum.

Over the past several years, the field of medical genetics has continued to expand and is now impacting a broad range of medical care, mainly due to rapid advances in genetic technology and information generated by the Human Genome Project. Physicians from multiple disciplines will need to become familiar with genetic principles, and the availability of genetic databases on the internet is a valuable resource for medical students and physicians. To integrate these tools into medical student training, the University of Chicago Pritzker School of Medicine set out to develop multiple, interactive, case-based, educational sessions in the pre-clinical and clinical curriculum, designed to reinforce basic principles taught in the pre-clinical genetics class and demonstrate the usefulness of genetic information accessible via the internet in the clinical setting.

NSD1 analysis for Sotos syndrome: insights and perspectives from the clinical laboratory.

Purpose: Sotos syndrome is a genetic disorder characterized primarily by overgrowth, developmental delay, and a characteristic facial gestalt. Defects in the NSD1 gene are present in approximately 80% of patients with Sotos syndrome. The goal of this study was to determine the incidence of NSD1 abnormalities in patients referred to a clinical laboratory for testing and to identify clinical criteria that distinguish between patients with and without NSD1 abnormalities.