Activated phosphoinositide 3-kinase δ syndrome associated with nephromegaly, growth hormone deficiency, bronchiectasis: a case report
Allergy Asthma Clin Immunol. 2022 Feb 21;18(1):15. doi: 10.1186/s13223-022-00655-5. ABSTRACT BACKGROUND: Activated phosphoinositide 3-kinase (PI3K) δ syndrome (APDS) is a rare form of primary immunodeficiency with 243 known cases reported in the literature. Known findings associated with the condition include recurrent sinusitis and bronchitis, bronchiectasis, immune cytopenias, mild developmental delay, splenomegaly, and lymphadenopathy. We report […]
Expanding the phenotypic and molecular spectrum of NFS1-related disorders that cause functional deficiencies in mitochondrial and cytosolic iron-sulfur cluster containing enzymes
Hum Mutat. 2022 Jan 13. doi: 10.1002/humu.24330. Online ahead of print. ABSTRACT Iron-sulfur cluster proteins are involved in critical functions for gene expression regulation and mitochondrial bioenergetics including the oxidative phosphorylation system. The c.215G>A p.(Arg72Gln) variant in NFS1 has been previously reported to cause infantile mitochondrial complex II and III deficiency. We describe three additional […]
DNA methylation episignature in Gabriele-de Vries syndrome
Genet Med. 2022 Jan 10:S1098-3600(21)05422-8. doi: 10.1016/j.gim.2021.12.003. Online ahead of print. ABSTRACT PURPOSE: Gabriele-de Vries syndrome (GADEVS) is a rare genetic disorder characterized by developmental delay and/or intellectual disability, hypotonia, feeding difficulties, and distinct facial features. To refine the phenotype and to better understand the molecular basis of the syndrome, we analyzed clinical data and […]
AHDC1 missense mutations in Xia-Gibbs syndrome
HGG Adv. 2021 Oct 14;2(4):100049. doi: 10.1016/j.xhgg.2021.100049. Epub 2021 Aug 10. ABSTRACT Xia-Gibbs syndrome (XGS; MIM: 615829) is a phenotypically heterogeneous neurodevelopmental disorder (NDD) caused by newly arising mutations in the AT-Hook DNA-Binding Motif-Containing 1 (AHDC1) gene that are predicted to lead to truncated AHDC1 protein synthesis. More than 270 individuals have been diagnosed with […]
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 […]