Genetics professionals' attitudes toward prenatal exome sequencing.

Prenatal exome sequencing (ES) currently has limited use in the clinical setting, but research suggests that it has added diagnostic utility over karyotyping and array techniques for prenatal diagnosis of fetuses presenting with ultrasound abnormalities. The purpose of this study was to assess the attitudes of genetics professionals toward the clinical implementation of prenatal ES in order to guide development of professional guidelines. A survey was developed using themes identified in previous qualitative studies and was distributed to members of the American College of Medical Genetics and Genomics (ACMG), the American Society of Human Genetics (ASHG), and the National Society of Genetic Counselors (NSGC). A total of 498 participants completed some portion of the survey. There was consensus among participants that there would be clinical utility of prenatal ES when used for diagnosis, pregnancy management, and termination decisions. The majority also agreed that prenatal ES was distinct from its current use in the pediatric and adult settings. There were many areas of contention regarding which types of results should be returned to families and whether or not the current ACMG guidelines for return of incidental findings should also apply to the prenatal setting. Overall, professional guidance is needed to address the continuing concerns surrounding prenatal ES as its utilization in this setting is expected to grow.

Clinical diagnostic exome evaluation for an infant with a lethal disorder: genetic diagnosis of TARP syndrome and expansion of the phenotype in a patient with a newly reported RBM10 alteration.

BACKGROUND: Diagnostic Exome Sequencing (DES) has been shown to be an effective tool for diagnosis individuals with suspected genetic conditions. CASE PRESENTATION: We report a male infant born with multiple anomalies including bilateral dysplastic kidneys, cleft palate, bilateral talipes, and bilateral absence of thumbs and first toes. Prenatal testing including chromosome analysis and microarray did not identify a cause for the multiple congenital anomalies. Postnatal diagnostic exome studies (DES) were utilized to find a molecular diagnosis for the patient. Exome sequencing of the proband, mother, and father showed a previously unreported maternally inherited RNA binding motif protein 10 (RBM10) c.1352_1353delAG (p.E451Vfs*66) alteration. Mutations in RBM10 are associated with TARP syndrome, an X-linked recessive disorder originally described with cardinal features of talipes equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava. CONCLUSION: DES established a molecular genetic diagnosis of TARP syndrome for a neonatal patient with a poor prognosis in whom traditional testing methods were uninformative and allowed for efficient diagnosis and future reproductive options for the parents. Other reported cases of TARP syndrome demonstrate significant variability in clinical phenotype. The reported features in this infant including multiple hemivertebrae, imperforate anus, aplasia of thumbs and first toes have not been reported in previous patients, thus expanding the clinical phenotype for this rare disorder.

Storage and use of Newborn Screening Blood Specimens for Research: Assessing Public Opinion in Illinois.

Storage and use of residual dried blood spots (DBS) from newborn screening (NBS) for research purposes has been a topic of elevated interest following high profile disputes between genetic privacy advocacy groups and state NBS programs. Our objective was to assess public opinion in Illinois regarding storage and use of residual DBS for research. Five hundred twenty-six Illinois residents completed a survey assessing attitudes about research uses for DBS, storage length, and consent issues. Over 80 % of respondents expressed agreement with questions regarding research uses of DBS. Eighty-three percent of respondents were in favor of storage for at least one year with 44 % favoring indefinite storage. Respondents with higher educational attainment were more likely to support research use of DBS and less likely to desire contact for each future study (P < 0.05). Black respondents were less likely than white respondents to express agreement for the use of DBS for research or to favor long-term storage (P < 0.05). Support was high for storage and use of DBS in our sample. Consent was important and respondents wanted choices about participation. Forty-two percent of respondents were not aware of NBS prior to this survey, highlighting a need for greater education about this public health program. Trust in the public health service of NBS must be protected through transparency in the policy process.

Mosaic Trisomy 16 Associated with Left Lung Agenesis, Abnormal Left Arm, and Right Pulmonary Artery Stenosis: Expanding the Phenotype and Review of the Literature.

Trisomy 16 is the most common autosomal trisomy found in spontaneous abortions with mosaic versions seen in survivors. However, surviving children have multiple congenital defects and are at risk of growth and developmental delay. We report an additional case of mosaic trisomy 16 diagnosed by amniocentesis and confirmed after birth. Our patient is the first documented case of living mosaic trisomy 16 with the malformation constellation of lung agenesis, left pulmonary artery agenesis, congenital heart defects, and ipsilateral radial ray and limb abnormalities, expanding the phenotype of this rare condition. Additionally, this individual's unique combination of lung and cardiac defects caused morbidities that were challenging to manage and complicated family counseling as well.