Clinical whole-exome sequencing results impact medical management.

Background: Clinical diagnostic whole-exome sequencing (WES) is a powerful tool for patients with undiagnosed genetic disorders. To demonstrate the clinical utility, we surveyed healthcare providers (HCP) about changes in medical management and treatment, diagnostic testing, reproductive planning, and use of educational services subsequent to WES testing.

Methods: For a period of 18 months, an 18-question survey was sent to HCPs attached to the WES reports.

Postmortem Diagnostic Exome Sequencing Identifies a De Novo TUBB3 Alteration in a Newborn With Prenatally Diagnosed Hydrocephalus and Suspected Walker-Warburg Syndrome.

Objective Herein, we report a case of a deceased newborn with prenatally detected hydrocephalus. Postnatal findings included abnormal brain imaging and electroencephalogram, optic nerve abnormalities, and elevated creatine kinase (CK). No underlying genetic etiology had been previously identified for the proband, despite testing with a congenital muscular dystrophy gene panel.

Diagnostic exome sequencing for patients with a family history of consanguinity: over 38% of positive results are not autosomal recessive pattern.

Diagnostic exome sequencing (DES) is an effective tool for diagnosis in intractable cases where the underlying cause is thought be genetic. It is commonly assumed that patients with a family history of consanguinity will have increased detection rates for rare autosomal recessive Mendelian disorders through DES. Herein, we analyzed the diagnostic yield and relevant inheritance patterns within the DES cases with a reported consanguineous family history.

Exome sequencing positively identified relevant alterations in more than half of cases with an indication of prenatal ultrasound anomalies.

Objective: Exome sequencing is a successful option for diagnosing individuals with previously uncharacterized genetic conditions, however little has been reported regarding its utility in a prenatal setting. The goal of this study is to describe the results from a cohort of fetuses for which exome sequencing was performed.

Methods: We performed a retrospective analysis of the first seven cases referred to our laboratory for exome sequencing following fetal demise or termination of pregnancy.

Nearly a third of abnormalities found after first-trimester screening are different than expected: 10-year experience from a single center.

Objective: This study aimed to assess the efficacy of first-trimester aneuploidy screening in a single clinical setting.

Methods: Maternal age, nuchal translucency, and maternal serum levels of pregnancy-associated plasma protein A and free beta human chorionic gonadotrophin comprised first-trimester risk assessment for Down syndrome and trisomies 13/18. Means, screen positive rates, detection rates, and predictive values were calculated for Down syndrome and trisomies 13/18.

Increased nuchal translucency in the presence of normal chromosomes: what's next?

Purpose Of Review: First trimester screening is presently offered to all pregnant women as a means of prenatal screening for Down syndrome, trisomy 18, and trisomy 13. Nuchal translucency measurement is a fundamental component of the screening protocol. A woman whose fetus' nuchal translucency is greater than the 95th percentile is also at increased risk for a multiplicity of other adverse pregnancy and pediatric outcomes, and as a consequence, counseling of patients about their testing options and range of pregnancy outcomes has become complex and difficult.

Genetic assessment following increased nuchal translucency and normal karyotype.

Objective: The objective of this study was to assess the first formal approach for monitoring genetic/developmental syndromes associated with the presence of an increased nuchal translucency (NT) thickness (>3 mm) in the first trimester of pregnancy.

Methods: Multiple technologies-a DNA chip using the APEX technology, qPCR, microfluidic PCR, and sequencing-were applied to assay 310 mutations across five conditions-Noonan syndrome, congenital adrenal hyperplasia, spinal muscular atrophy (SMA), DiGeorge syndrome, and Smith-Lemli Opitz syndrome.

Results: We report the results of assessing the first 120 patients in which 8 cases of Noonan syndrome were detected as well as an unusually high rate of heterozygosity for SMA.