INTRODUCTION: Fanconi Anemia Type C (FAC) is an autosomal recessive disorder characterized by skeletal malformations, bone marrow failure, increased risk of malignancy, and severe aplastic anemia. Currently, carrier testing for FAC is recommended for the Ashkenazi Jewish (AJ) population. A joint ACOG/ACMG statement highlighted the increasingly multi-ethnic society as consideration for pan-ethnic carrier testing, and recent ACOG committee opinion states that pan-ethnic testing is a reasonable strategy. Our current study assesses how many non-AJ individuals screened positive for FAC when pan-ethnic carrier testing was implemented. METHODS: Retrospective database analysis of individuals that received expanded carrier testing utilizing a genotyping panel for three pathologic variants of FAC (c.322delG, IVS4 c.456(+4)A>T, p.R548X) was performed. Expected number of positive carriers in AJ and non-AJ groups were calculated and compared to observed rates. Chi-square analysis was performed to assess for statistical significance (p < 0.01). RESULTS: A total of 71,235 individuals were tested for FAC. A higher than expected number of non-AJ individuals tested positive for FAC (56 observed vs 8.89 expected, p<0.001). The number of AJ individuals that screened positive was consistent with expected values (10 observed vs 11.11 expected, p<0.73). CONCLUSION: Non-AJ carriers of FAC were more common than expected in this cohort. Pan-ethnic expanded carrier testing will increase the detection of carriers for FAC compared with current ethnicity based screening recommendations. Importantly, carriers of FAC who would be missed by ethnicity based testing convention, will be identified allowing for more complete genetic counseling and family planning options for those who choose testing.

ObjectivesExpanded carrier testing is acknowledged as an acceptable strategy for carrier testing by the American College of Obstetrics and Gynecology. Limited studies have investigated positivity rates of expanded carrier panels. We describe our experience with 3 commercial laboratory panels varying in size from 3 to 218 disorders.MethodsWe reviewed outcomes for 3 multigene carrier screening panels: trio (3 diseases), standard (23 diseases), and global (218 diseases). All panels used targeted genotype analysis of preselected mutations via next‐generation sequencing. We calculated positivity rates for each panel.ResultsPositivity rates were 7.2% for Preparent Trio, 13.2% for Preparent Standard, and 35.8% for Preparent Global. The most frequent positive results in the global panel were (in descending order): abnormal hemoglobin electrophoresis, familial Mediterranean fever, cystic fibrosis, fragile X, glucose‐6‐phosphate dehydrogenase deficiency, alpha‐thalassemia, and nonsyndromic hearing loss.ConclusionsWhile genetic diseases are individually rare, they are cumulatively common. Our experience illustrates that, with a panel of 218 diseases, the likelihood of identifying a carrier can be as high as 36%. Understanding panel positivity rates is one important factor for providers when choosing the right test for their practice, setting appropriate expectations for patients, and planning for follow‐up counseling.

INTRODUCTION: ACOG guidelines recommend red blood cell indices followed by hemoglobin electrophoresis to assess carrier status for hemoglobinopathies. However, data is limited on outcomes of these recommendations, and the role of DNA testing. METHODS: Our database was queried for abnormal hemoglobin evaluations from 42,166 consecutive samples of mixed ethnicities. Hemoglobin evaluation consisted of red blood indices and, high-performance liquid chromatography followed by, if necessary, hemoglobin electrophoresis. A subset (n= 2,863) also had DNA genotyping. Abnormal reports were evaluated individually, and test metrics and interpretations were tabulated. RESULTS: Of the 42,166 samples, 2,278 (5.4%) had abnormal hemoglobin evaluation results. Of the 2,278 abnormal results, the most common interpretation (32%) was 'possible alpha thalassemia trait', followed by 'sickle cell trait' (22%), 'possible beta thalassemia trait' (10%), 'elevated hemoglobin F' (10%), and 'hemoglobin C trait' (5%). Of the 2,863 samples that had genotyping, 146 (5.1%) had abnormal molecular results. Genotyping confirmed 100% (5/5) of samples with abnormal hemoglobin evaluation indicating 'consistent with alpha thalassemia trait' and 41% (17/41) indicating 'possible alpha thalassemia trait'. Sixteen percent (14/89) of samples with abnormal molecular results, and normal hemoglobin evaluation for alpha thalassemia, were silent alpha thalassemia carriers. CONCLUSION: Our study estimates a 5% positivity rate for hemoglobin evaluation. However, some results are non-specific and require molecular follow up. Forty-one percent of hemoglobin evaluation results interpreted as 'possible alpha thalassemia trait' were confirmed as genetic carriers. Concurrent DNA testing provides information and results more quickly to patients, and better identifies those patients truly at risk to be carriers of alpha thalassemia.

INTRODUCTION: Expanded genetic carrier testing allows couples to determine their reproductive risk for genetic disorders regardless of an individual's ancestral background or geographic origin. METHODS: As part of routine laboratory management, requisitions were reviewed for information on reproductive partners. Our database was queried for names of reproductive partners, and demographic information was cross-referenced to determine validity of the matched sample. A retrospective analysis was performed for known matched reproductive pairs and descriptive analysis regarding ethnicity, test ordered, and results of genetic carrier testing on each matched pair was performed. RESULTS: Data was entered for 1,585 reproductive partners; after validation and confirmation of carrier testing performed, 783 known reproductive pairs were confirmed. Forty-six (5.9%) couples were found to be at risk for the same autosomal recessive disorder(s), including: hereditary hemochromatosis (20), cystic fibrosis (10), familial Mediterranean fever (6), hemoglobinopathies (5), spinal muscular atrophy (3), primary congenital glaucoma (2), and phenylalanine hydroxylase deficiency (PKU) (1). An additional 1% were potentially at increased risk for the same genetic disorder due to indeterminate results by enzyme analysis or hemoglobin electrophoresis. CONCLUSION: Our study identified 6.9% of couples to be at increased risk to have an affected child, and demonstrates the importance of testing partners to allow for reproductive decision-making. Additionally, 28 (61%) of these couples were found to be carriers of disorders only included on expanded carrier testing panels. Therefore, testing patients with an expanded pan-ethnic panel will identify more couples at risk for disorders that would be missed by current ethnicity-based recommendations.

INTRODUCTION: Expanded carrier testing is recognized by ACOG as an acceptable testing strategy in women’s healthcare. We report a large OB/GYN practice’s experience with expanded carrier testing including partner testing uptake and reproductive risk. METHODS: A retrospective analysis of expanded carrier testing ordered at a multi-provider clinic was performed. Data analyzed included patient demographics, testing outcomes, and reproductive risks. RESULTS: Out of 537 female patients tested, 265 (49.3%) were positive; of those, 201 (75.8%) had partner testing. Fourteen (7.0%) couples were at risk to have a child affected with an autosomal recessive disorder (8 hemochromatosis, 3 familial Mediterranean fever, 1 PKU, 1 primary congenital glaucoma, 1 GJB2 non-syndromic hearing loss). Thirty women were carriers of an X-linked disorder (22 G6PD, 7 Fragile X premutation, and 1 GJB1-related Charcot-Marie Tooth disease). Incidentally, 10 patients were found who may have symptoms of a genetic condition based on their genotype (5 G6PD, 4 hemochromatosis, 1 carnitine palmitoyltransferase II deficiency), which could impact patient and pregnancy management. CONCLUSION: Implementing an expanded carrier testing protocol including partner testing identifies carriers of many disorders and allows for reproductive risk identification. In this cohort, out of 537 patients who were tested, 43 (8.0%) were identified to have reproductive risk either due to an X-linked disorder or as carriers of the same autosomal recessive disorder. Risk identification empowers patients to make informed decisions with the guidance of their provider. This experience demonstrates the yield of expanded carrier testing when routine testing and partner follow-up is incorporated in a busy obstetrical practice.