Phenotypic Spectrum in a Family Sharing a Heterozygous Variant.

Background And Purpose: Mutations in have classically been associated with benign familial neonatal and infantile seizures and more recently identified in patients with neurodevelopmental disorders and abnormal electroencephalogram (EEG) findings. We present 4 affected patients from a family with a pathogenic mutation in with a unique constellation of clinical findings.

Methods: A family of 3 affected siblings and mother sharing a pathogenic variant are described, including clinical history, genetic results, and EEG and magnetic resonance imaging (MRI) findings.

Novel truncating variant in associated with cerebellar hypoplasia and velopharyngeal dysfunction.

-related neurodevelopmental disorder is a recently described intellectual disability syndrome often with speech difficulties. Here, we describe an individual with a heterozygous frameshift variant in (NM_182931.2:c.

Inherited and de novo variants extend the etiology of -associated neurodevelopmental disorder.

Alterations in the gene have recently emerged as the cause of developmental delay with or without intellectual impairment or behavioral abnormalities (MIM # 619575). The 32 cases currently described in the literature have predominantly de novo alterations in and a wide spectrum of neurodevelopmental abnormalities. Here, we report four patients with novel pathogenic variants identified by research genome sequencing, clinical exome sequencing, and international matchmaking.

De novo variants in H3-3A and H3-3B are associated with neurodevelopmental delay, dysmorphic features, and structural brain abnormalities.

The histone H3 variant H3.3, encoded by two genes H3-3A and H3-3B, can replace canonical isoforms H3.1 and H3.

A qualitative assessment of parental experiences with false-positive newborn screening for Krabbe disease.

Numerous US states have implemented newborn screening for Krabbe disease (Krabbe NBS) as a result of legislative state mandates. While healthcare provider opinions toward Krabbe NBS have been documented, few studies have explored parental experiences and opinions regarding Krabbe NBS. Eleven families, who received a false-positive Krabbe NBS result and received genetic counseling at an institution in central Ohio, were consented to participate in semistructured interviews.

Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I.

Enzyme-based newborn screening for Mucopolysaccharidosis type I (MPS I) has a high false-positive rate due to the prevalence of pseudodeficiency alleles, often resulting in unnecessary and costly follow up. The glycosaminoglycans (GAGs), dermatan sulfate (DS) and heparan sulfate (HS) are both substrates for α-l-iduronidase (IDUA). These GAGs are elevated in patients with MPS I and have been shown to be promising biomarkers for both primary and second-tier testing.