Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2 Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder.

NTNG2 encodes netrin-G2, a membrane-anchored protein implicated in the molecular organization of neuronal circuitry and synaptic organization and diversification in vertebrates. In this study, through a combination of exome sequencing and autozygosity mapping, we have identified 16 individuals (from seven unrelated families) with ultra-rare homozygous missense variants in NTNG2; these individuals present with shared features of a neurodevelopmental disorder consisting of global developmental delay, severe to profound intellectual disability, muscle weakness and abnormal tone, autistic features, behavioral abnormalities, and variable dysmorphisms. The variants disrupt highly conserved residues across the protein.

The utilization of prenatal microarray: A survey of current genetic counseling practices and barriers.

Objective: We evaluated what prenatal genetic counselor's (GCs) practices, attitudes, and barriers are in regards to prenatal microarray since the publication of the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) guidelines for microarray use.

Methods: This was a survey-based cross-sectional study of English-speaking, board certified or eligible GCs who currently practice prenatal genetic counseling.

Results: Of 192 respondents, 183 (95%) have incorporated chromosome microarray (CMA) into clinical practice, with 64% believing that the benefits of CMA outweigh the harms and 52% agreeing that CMA should be offered to all women regardless of indication.

Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic.

Despite the potential of whole-genome sequencing (WGS) to improve patient diagnosis and care, the empirical value of WGS in the cancer genetics clinic is unknown. We performed WGS on members of two cohorts of cancer genetics patients: those with mutations (n = 176) and those without (n = 82). Initial analysis of potentially pathogenic variants (PPVs, defined as nonsynonymous variants with allele frequency < 1% in ESP6500) in 163 clinically-relevant genes suggested that WGS will provide useful clinical results.