Characterization of a patient-derived variant of GPX4 for precision therapy
Nat Chem Biol. 2021 Dec 20. doi: 10.1038/s41589-021-00915-2. Online ahead of print. ABSTRACT Glutathione peroxidase 4 (GPX4), as the only enzyme in mammals capable of reducing esterified phospholipid hydroperoxides within a cellular context, protects cells from ferroptosis. We identified a homozygous point mutation in the GPX4 gene, resulting in an R152H coding mutation, in three […]
Development of therapies for rare genetic disorders of GPX4: roadmap and opportunities
Orphanet J Rare Dis. 2021 Oct 23;16(1):446. doi: 10.1186/s13023-021-02048-0. ABSTRACT BACKGROUND: Extremely rare progressive diseases like Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) can be neonatally lethal and therefore go undiagnosed or are difficult to treat. Recent sequencing efforts have linked this disease to mutations in GPX4, with consequences in the resulting enzyme, glutathione peroxidase 4. This offers […]
Artificial intelligence enables comprehensive genome interpretation and nomination of candidate diagnoses for rare genetic diseases
Genome Med. 2021 Oct 14;13(1):153. doi: 10.1186/s13073-021-00965-0. ABSTRACT BACKGROUND: Clinical interpretation of genetic variants in the context of the patient’s phenotype is becoming the largest component of cost and time expenditure for genome-based diagnosis of rare genetic diseases. Artificial intelligence (AI) holds promise to greatly simplify and speed genome interpretation by integrating predictive methods with […]
Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines
Nat Commun. 2021 Sep 20;12(1):5529. doi: 10.1038/s41467-021-25515-5. ABSTRACT Inherited disorders of neurotransmitter metabolism are rare neurodevelopmental diseases presenting with movement disorders and global developmental delay. This study presents the results of the first standardized deep phenotyping approach and describes the clinical and biochemical presentation at disease onset as well as diagnostic approaches of 275 patients […]
Commentary: Galactosemia Diagnosis by Whole Exome Sequencing Later in Life
Mov Disord Clin Pract. 2021 Sep 3;8(Suppl 1):S40-S41. doi: 10.1002/mdc3.13304. eCollection 2021 Aug. NO ABSTRACT PMID:34514047 | PMC:PMC8414503 | DOI:10.1002/mdc3.13304
Maternal Smoking and Congenital Heart Defects, National Birth Defects Prevention Study, 1997-2011
J Pediatr. 2021 Sep 8:S0022-3476(21)00877-5. doi: 10.1016/j.jpeds.2021.09.005. Online ahead of print. ABSTRACT OBJECTIVES: To assess associations between maternal smoking and congenital heart defects (CHDs) in offspring. STUDY DESIGN: We performed a retrospective case-control study using data for cases of CHD (n=8,339) and non-malformed controls (n=11,020) children from all years (1997-2011) of the National Birth Defects […]
To Be or No B2: A Rare Cause of Stridor and Weakness in a Toddler
Child Neurol Open. 2021 Aug 5;8:2329048X211030723. doi: 10.1177/2329048X211030723. eCollection 2021 Jan-Dec. ABSTRACT We present a case of a young child with a rare metabolic disorder whose clinical presentation resembled that of autoimmune myasthenia gravis. The differential diagnosis was expanded when autoantibody testing was negative and the patient did not respond to standard immunomodulatory therapies. Rapid […]
Exome sequencing of child-parent trios with bladder exstrophy: Findings in 26 children
Am J Med Genet A. 2021 Aug 5. doi: 10.1002/ajmg.a.62439. Online ahead of print. ABSTRACT Bladder exstrophy (BE) is a rare, lower ventral midline defect with the bladder and part of the urethra exposed. The etiology of BE is unknown but thought to be influenced by genetic variation with more recent studies suggesting a role […]
Use of Metagenomic Next-Generation Sequencing to Identify Pathogens in Pediatric Osteoarticular Infections
Open Forum Infect Dis. 2021 Jul 17;8(7):ofab346. doi: 10.1093/ofid/ofab346. eCollection 2021 Jul. ABSTRACT BACKGROUND: Osteoarticular infections (OAIs) are frequently encountered in children. Treatment may be guided by isolation of a pathogen; however, operative cultures are often negative. Metagenomic next-generation sequencing (mNGS) allows for broad and sensitive pathogen detection that is culture-independent. We sought to evaluate […]
Ending a diagnostic odyssey: Moving from exome to genome to identify cockayne syndrome
Mol Genet Genomic Med. 2021 Jun 2:e1623. doi: 10.1002/mgg3.1623. Online ahead of print. ABSTRACT BACKGROUND: Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized by growth failure and multisystemic degeneration. Excision repair cross-complementation group 6 (ERCC6 OMIM: *609413) is the gene most frequently mutated in CS. METHODS: A child with pre and postnatal growth […]