Early Newborn Metabolic Patterning and Sudden Infant Death Syndrome
JAMA Pediatr. 2024 Sep 9. doi: 10.1001/jamapediatrics.2024.3033. Online ahead of print. ABSTRACT IMPORTANCE: Sudden infant death syndrome (SIDS) is a major cause of infant death in the US. Previous research suggests that inborn errors of metabolism may contribute to SIDS, yet the relationship between SIDS and biomarkers of metabolism remains unclear. OBJECTIVE: To evaluate and […]
Parent and patient knowledge and attitudes about cancer predisposition syndrome genetic testing in pediatric oncology: Understanding sociodemographic and parent-child differences
Cancer Rep (Hoboken). 2024 Sep;7(9):e2119. doi: 10.1002/cnr2.2119. ABSTRACT BACKGROUND: Cancer predisposition syndromes (CPS) impact about 10% of patients with pediatric cancer. Genetic testing (CPS-GT) has multiple benefits, but few studies have described parent and child knowledge and attitudes regarding CPS-GT decision-making. This study examined parent and patient CPS-GT decision-making knowledge and attitudes. PROCEDURE: English- or […]
Clinical and neuroradiological spectrum of biallelic variants in NOTCH3
EBioMedicine. 2024 Aug 26;107:105297. doi: 10.1016/j.ebiom.2024.105297. Online ahead of print. ABSTRACT BACKGROUND: NOTCH3 encodes a transmembrane receptor critical for vascular smooth muscle cell function. NOTCH3 variants are the leading cause of hereditary cerebral small vessel disease (SVD). While monoallelic cysteine-involving missense variants in NOTCH3 are well-studied in cerebral autosomal dominant arteriopathy with subcortical infarcts and […]
Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy
Nat Commun. 2024 Aug 22;15(1):7239. doi: 10.1038/s41467-024-51310-z. ABSTRACT Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A […]
Antisense oligonucleotide therapy in an individual with KIF1A-associated neurological disorder
Nat Med. 2024 Aug 9. doi: 10.1038/s41591-024-03197-y. Online ahead of print. ABSTRACT KIF1A-associated neurological disorder (KAND) is a neurodegenerative and often lethal ultrarare disease with a wide phenotypic spectrum associated with largely heterozygous de novo missense variants in KIF1A. Antisense oligonucleotide treatments represent a promising approach for personalized treatments in ultrarare diseases. Here we report […]
Severe Acute Motor Exacerbations (SAME) across Metabolic, Developmental and Genetic Disorders
Mov Disord. 2024 Aug 9. doi: 10.1002/mds.29905. Online ahead of print. ABSTRACT Acute presentation of severe motor disorders is a diagnostic and management challenge. We define severe acute motor exacerbations (SAME) as acute/subacute motor symptoms that persist for hours-to-days with a severity that compromise vital signs (temperature, breath, and heart rate) and bulbar function (swallowing/dysphagia). […]
The growing research toolbox for SLC13A5 citrate transporter disorder: a rare disease with animal models, cell lines, an ongoing Natural History Study and an engaged patient advocacy organization
Ther Adv Rare Dis. 2024 Jul 31;5:26330040241263972. doi: 10.1177/26330040241263972. eCollection 2024 Jan-Dec. ABSTRACT TESS Research Foundation (TESS) is a patient-led nonprofit organization seeking to understand the basic biology and clinical impact of pathogenic variants in the SLC13A5 gene. TESS aims to improve the fundamental understanding of citrate’s role in the brain, and ultimately identify treatments […]
MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature
Am J Hum Genet. 2024 May 28:S0002-9297(24)00164-2. doi: 10.1016/j.ajhg.2024.05.001. Online ahead of print. ABSTRACT Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent […]
Biallelic Loss of Function Variants in SENP7 Cause Immunodeficiency with Neurologic and Muscular Phenotypes
J Pediatr. 2024 Jul 4:114180. doi: 10.1016/j.jpeds.2024.114180. Online ahead of print. ABSTRACT To evaluate a novel candidate disease gene, we engaged international collaborators and identified rare, biallelic, specifically homozygous, loss of function variants in SENP7 in four children from three unrelated families presenting with neurodevelopmental abnormalities, dysmorphism, and immunodeficiency. Their clinical presentations were characterized by […]
Genome Sequencing for Diagnosing Rare Diseases
N Engl J Med. 2024 Jun 6;390(21):1985-1997. doi: 10.1056/NEJMoa2314761. ABSTRACT BACKGROUND: Genetic variants that cause rare disorders may remain elusive even after expansive testing, such as exome sequencing. The diagnostic yield of genome sequencing, particularly after a negative evaluation, remains poorly defined. METHODS: We sequenced and analyzed the genomes of families with diverse phenotypes who […]