Assessing Diversity in Newborn Genomic Sequencing Research Recruitment: Race/Ethnicity and Primary Spoken Language Variation in Eligibility, Enrollment, and Reasons for Declining
Clin Ther. 2023 Jul 8:S0149-2918(23)00220-5. doi: 10.1016/j.clinthera.2023.06.014. Online ahead of print. ABSTRACT PURPOSE: Diagnostic genomic research has the potential to directly benefit participants. This study sought to identify barriers to equitable enrollment of acutely ill newborns into a diagnostic genomic sequencing research study. METHODS: We reviewed the 16-month recruitment process of a diagnostic genomic research […]
Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness
Sci Adv. 2023 Jun 30;9(26):eadf2860. doi: 10.1126/sciadv.adf2860. Epub 2023 Jun 30. ABSTRACT Cell cycle dysregulation is prerequisite for cancer formation. However, it is unknown whether the mode of dysregulation affects disease characteristics. Here, we conduct comprehensive analyses of cell cycle checkpoint dysregulation using patient data and experimental investigations. We find that ATM mutation predisposes the […]
Biallelic loss of function variants in WBP4 , encoding a spliceosome protein, result in a variable neurodevelopmental delay syndrome
medRxiv. 2023 Jun 27:2023.06.19.23291425. doi: 10.1101/2023.06.19.23291425. Preprint. ABSTRACT Over two dozen spliceosome proteins are involved in human diseases, also referred to as spliceosomopathies. WBP4 (WW Domain Binding Protein 4) is part of the early spliceosomal complex, and was not described before in the context of human pathologies. Ascertained through GeneMatcher we identified eleven patients from […]
BRAT1-related disorders: phenotypic spectrum and phenotype-genotype correlations from 97 patients
Eur J Hum Genet. 2023 Jun 21. doi: 10.1038/s41431-023-01410-z. Online ahead of print. ABSTRACT BRAT1 biallelic variants are associated with rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL), and neurodevelopmental disorder associating cerebellar atrophy with or without seizures syndrome (NEDCAS). To date, forty individuals have been reported in the literature. We collected clinical and molecular […]
A gene-based association test of interactions for maternal-fetal genotypes identifies genes associated with nonsyndromic congenital heart defects
Genet Epidemiol. 2023 Jun 21. doi: 10.1002/gepi.22533. Online ahead of print. ABSTRACT The risk of congenital heart defects (CHDs) may be influenced by maternal genes, fetal genes, and their interactions. Existing methods commonly test the effects of maternal and fetal variants one-at-a-time and may have reduced statistical power to detect genetic variants with low minor […]
Response to Grosse et al
Am J Hum Genet. 2023 Jun 1;110(6):1017. doi: 10.1016/j.ajhg.2023.05.004. NO ABSTRACT PMID:37267897 DOI:10.1016/j.ajhg.2023.05.004
Variant STAT4 and Response to Ruxolitinib in an Autoinflammatory Syndrome
N Engl J Med. 2023 May 31. doi: 10.1056/NEJMoa2202318. Online ahead of print. ABSTRACT BACKGROUND: Disabling pansclerotic morphea (DPM) is a rare systemic inflammatory disorder, characterized by poor wound healing, fibrosis, cytopenias, hypogammaglobulinemia, and squamous-cell carcinoma. The cause is unknown, and mortality is high. METHODS: We evaluated four patients from three unrelated families with an […]
Heteromeric clusters of ubiquitinated ER-shaping proteins drive ER-phagy
Nature. 2023 May 24. doi: 10.1038/s41586-023-06090-9. Online ahead of print. ABSTRACT Membrane-shaping proteins characterized by reticulon homology domains play an important part in the dynamic remodelling of the endoplasmic reticulum (ER). An example of such a protein is FAM134B, which can bind LC3 proteins and mediate the degradation of ER sheets through selective autophagy (ER-phagy)1. […]
AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model
Acta Neuropathol. 2023 Apr 29. doi: 10.1007/s00401-023-02579-9. Online ahead of print. ABSTRACT Hereditary spastic paraplegias (HSP) are rare, inherited neurodegenerative or neurodevelopmental disorders that mainly present with lower limb spasticity and muscle weakness due to motor neuron dysfunction. Whole genome sequencing identified bi-allelic truncating variants in AMFR, encoding a RING-H2 finger E3 ubiquitin ligase anchored […]
The genomic landscape of familial glioma
Sci Adv. 2023 Apr 28;9(17):eade2675. doi: 10.1126/sciadv.ade2675. Epub 2023 Apr 28. ABSTRACT Glioma is a rare brain tumor with a poor prognosis. Familial glioma is a subset of glioma with a strong genetic predisposition that accounts for approximately 5% of glioma cases. We performed whole-genome sequencing on an exploratory cohort of 203 individuals from 189 […]