A founder mutation in PEX12 among Egyptian patients in peroxisomal biogenesis disorder
Neurol Sci. 2020 Oct 29. doi: 10.1007/s10072-020-04843-2. Online ahead of print. ABSTRACT At least 14 distinctive PEX genes function in the biogenesis of peroxisomes. Biallelic alterations in the peroxisomal biogenesis factor 12 (PEX12) gene lead to Zellweger syndrome spectrum (ZSS) with variable clinical expressivity ranging from early lethality to mildly affected with long-term survival. Herein, […]
Rapid whole-genome sequencing identifies a homozygous novel variant, His540Arg, in HSD17B4 resulting in D-bifunctional protein deficiency disorder diagnosis
Cold Spring Harb Mol Case Stud. 2020 Dec 17;6(6):a005496. doi: 10.1101/mcs.a005496. Print 2020 Dec. ABSTRACT Rapid whole-genome sequencing (rWGS) allows for a diagnosis to be made quickly and impact medical management, particularly in critically ill children. Variants identified by this approach are often not identified using other testing methodologies, such as carrier screening or gene […]
ECHS1 disease in two unrelated families of Samoan descent: Common variant – rare disorder
Am J Med Genet A. 2021 Jan;185(1):157-167. doi: 10.1002/ajmg.a.61936. Epub 2020 Oct 28. ABSTRACT Mutations in the short-chain enoyl-CoA hydratase (SCEH) gene, ECHS1, cause a rare autosomal recessive disorder of valine catabolism. Patients usually present with developmental delay, regression, dystonia, feeding difficulties, and abnormal MRI with bilateral basal ganglia involvement. We present clinical, biochemical, molecular, […]
Best practices for the analytical validation of clinical whole-genome sequencing intended for the diagnosis of germline disease
NPJ Genom Med. 2020 Oct 23;5:47. doi: 10.1038/s41525-020-00154-9. eCollection 2020. ABSTRACT Whole-genome sequencing (WGS) has shown promise in becoming a first-tier diagnostic test for patients with rare genetic disorders; however, standards addressing the definition and deployment practice of a best-in-class test are lacking. To address these gaps, the Medical Genome Initiative, a consortium of leading […]
Insight into developmental mechanisms of global and focal migration disorders of cortical development
Curr Opin Neurobiol. 2020 Oct 21;66:77-84. doi: 10.1016/j.conb.2020.10.005. Online ahead of print. ABSTRACT Cortical development involves neurogenesis followed by migration, maturation, and myelination of immature neurons. Disruptions in these processes can cause malformations of cortical development (MCD). Radial glia (RG) are the stem cells of the brain, both generating neurons and providing the scaffold upon […]
Alternative genomic diagnoses for individuals with a clinical diagnosis of Dubowitz syndrome
Am J Med Genet A. 2021 Jan;185(1):119-133. doi: 10.1002/ajmg.a.61926. Epub 2020 Oct 24. ABSTRACT Dubowitz syndrome (DubS) is considered a recognizable syndrome characterized by a distinctive facial appearance and deficits in growth and development. There have been over 200 individuals reported with Dubowitz or a “Dubowitz-like” condition, although no single gene has been implicated as […]
Functional Precision Medicine Identifies New Therapeutic Candidates for Medulloblastoma
Cancer Res. 2020 Dec 1;80(23):5393-5407. doi: 10.1158/0008-5472.CAN-20-1655. Epub 2020 Oct 12. ABSTRACT Medulloblastoma is among the most common malignant brain tumors in children. Recent studies have identified at least four subgroups of the disease that differ in terms of molecular characteristics and patient outcomes. Despite this heterogeneity, most patients with medulloblastoma receive similar therapies, including […]
Innovative approach to identify multigenomic and environmental interactions associated with birth defects in family-based hybrid designs
Genet Epidemiol. 2021 Mar;45(2):171-189. doi: 10.1002/gepi.22363. Epub 2020 Sep 30. ABSTRACT Genes, including those with transgenerational effects, work in concert with behavioral, environmental, and social factors via complex biological networks to determine human health. Understanding complex relationships between causal factors underlying human health is an essential step towards deciphering biological mechanisms. We propose a new […]
Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia
Brain. 2020 Oct 1;143(10):2929-2944. doi: 10.1093/brain/awz307. ABSTRACT Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging […]
Detection of Neisseria gonorrhoeae from Joint Aspirate by Metagenomic Sequencing in Disseminated Gonococcal Infection
J Pediatric Infect Dis Soc. 2021 Apr 3;10(3):367-369. doi: 10.1093/jpids/piaa108. ABSTRACT Disseminated gonococcal infection (DGI) often manifests as gonococcal arthritis and may carry significant morbidity. However, diagnosis remains elusive due to limited sensitivity of available diagnostic tests. We used metagenomic next-generation sequencing to detect Neisseria gonorrhoeae from culture-negative joint aspirates of 2 patients with clinically […]