Prenatal Carrier Screening for Spinal Muscular Atrophy.

Introduction Spinal muscular atrophy (SMA), a neurodegenerative genetic disorder, affects 1:5,000 to 1:10,000 infants. Carrier rates are 1:25 to 1:50. We implemented ACOG-endorsed prenatal SMA screening in mid-2014 and sought to assess uptake, observed carrier rate, and providers' knowledge and attitudes toward genetic conditions and carrier screening.

De novo missense variants in HECW2 are associated with neurodevelopmental delay and hypotonia.

Background: The causes of intellectual disability (ID) are diverse and de novo mutations are increasingly recognised to account for a significant proportion of ID.

Methods And Results: In this study, we performed whole exome sequencing on a large cohort of patients with ID or neurodevelopmental delay and identified four novel de novo predicted deleterious missense variants in HECW2 in six probands with ID/developmental delay and hypotonia. Other common features include seizures, strabismus, nystagmus, cortical visual impairment and dysmorphic facial features.

Clinical features associated with copy number variations of the 14q32 imprinted gene cluster.

Uniparental disomy (UPD) for imprinted chromosomes can cause abnormal phenotypes due to absent or overexpression of imprinted genes. UPD(14)pat causes a unique constellation of features including thoracic skeletal anomalies, polyhydramnios, placentomegaly, and limited survival; its hypothesized cause is overexpression of paternally expressed RTL1, due to absent regulatory effects of maternally expressed RTL1as. UPD(14)mat causes a milder condition with hypotonia, growth failure, and precocious puberty; its hypothesized cause is absence of paternally expressed DLK1.