Biallelic loss of GNAS in a patient with pediatric medulloblastoma
Cold Spring Harb Mol Case Stud. 2019 Oct 23;5(5):a004572. doi: 10.1101/mcs.a004572. Print 2019 Oct. ABSTRACT Genome sequencing was performed on matched normal and tumor tissue from a 6.5-yr-old boy with a diagnosis of recurrent medulloblastoma. A pathogenic heterozygous c.432+1G>A canonical splice donor site variant in GNAS was detected on analysis of blood DNA. Analysis of […]
Dystonia-Ataxia with early handwriting deterioration in COQ8A mutation carriers: A case series and literature review
Parkinsonism Relat Disord. 2019 Nov;68:8-16. doi: 10.1016/j.parkreldis.2019.09.015. Epub 2019 Sep 28. ABSTRACT Cerebellar ataxia is a hallmark of coenzyme Q10 (CoQ10) deficiency associated with COQ8A mutations. We present four patients, one with novel COQ8A pathogenic variants all with early, prominent handwriting impairment, dystonia and only mild ataxia. To better define the phenotypic spectrum and course […]
Recurrent homozygous damaging mutation in TMX2, encoding a protein disulfide isomerase, in four families with microlissencephaly
J Med Genet. 2020 Apr;57(4):274-282. doi: 10.1136/jmedgenet-2019-106409. Epub 2019 Oct 5. ABSTRACT BACKGROUND: Protein disulfide isomerase (PDI) proteins are part of the thioredoxin protein superfamily. PDIs are involved in the formation and rearrangement of disulfide bonds between cysteine residues during protein folding in the endoplasmic reticulum and are implicated in stress response pathways. METHODS: Eight […]
Bi-allelic Loss of Human APC2, Encoding Adenomatous Polyposis Coli Protein 2, Leads to Lissencephaly, Subcortical Heterotopia, and Global Developmental Delay
Am J Hum Genet. 2019 Oct 3;105(4):844-853. doi: 10.1016/j.ajhg.2019.08.013. ABSTRACT Lissencephaly is a severe brain malformation in which failure of neuronal migration results in agyria or pachygyria and in which the brain surface appears unusually smooth. It is often associated with microcephaly, profound intellectual disability, epilepsy, and impaired motor abilities. Twenty-two genes are associated with […]
A Randomized, Controlled Trial of the Analytic and Diagnostic Performance of Singleton and Trio, Rapid Genome and Exome Sequencing in Ill Infants
Am J Hum Genet. 2019 Oct 3;105(4):719-733. doi: 10.1016/j.ajhg.2019.08.009. Epub 2019 Sep 26. ABSTRACT The second Newborn Sequencing in Genomic Medicine and Public Health study was a randomized, controlled trial of the effectiveness of rapid whole-genome or -exome sequencing (rWGS or rWES, respectively) in seriously ill infants with diseases of unknown etiology. Here we report […]
The mitochondrial carrier Citrin plays a role in regulating cellular energy during carcinogenesis
Oncogene. 2020 Jan;39(1):164-175. doi: 10.1038/s41388-019-0976-2. Epub 2019 Aug 28. ABSTRACT Citrin, encoded by SLC25A13 gene, is an inner mitochondrial transporter that is part of the malate-aspartate shuttle, which regulates the NAD+/NADH ratio between the cytosol and mitochondria. Citrullinemia type II (CTLN-II) is an inherited disorder caused by germline mutations in SLC25A13, manifesting clinically in growth […]
Bi-allelic GOT2 Mutations Cause a Treatable Malate-Aspartate Shuttle-Related Encephalopathy
Am J Hum Genet. 2019 Sep 5;105(3):534-548. doi: 10.1016/j.ajhg.2019.07.015. Epub 2019 Aug 15. ABSTRACT Early-infantile encephalopathies with epilepsy are devastating conditions mandating an accurate diagnosis to guide proper management. Whole-exome sequencing was used to investigate the disease etiology in four children from independent families with intellectual disability and epilepsy, revealing bi-allelic GOT2 mutations. In-depth metabolic […]
Agenesis of the putamen and globus pallidus caused by recessive mutations in the homeobox gene GSX2
Brain. 2019 Oct 1;142(10):2965-2978. doi: 10.1093/brain/awz247. ABSTRACT Basal ganglia are subcortical grey nuclei that play essential roles in controlling voluntary movements, cognition and emotion. While basal ganglia dysfunction is observed in many neurodegenerative or metabolic disorders, congenital malformations are rare. In particular, dysplastic basal ganglia are part of the malformative spectrum of tubulinopathies and X-linked […]
Hypospadias Prevalence and Trends in International Birth Defect Surveillance Systems, 1980-2010
Eur Urol. 2019 Oct;76(4):482-490. doi: 10.1016/j.eururo.2019.06.027. Epub 2019 Jul 9. ABSTRACT BACKGROUND: Hypospadias is a common male birth defect that has shown widespread variation in reported prevalence estimates. Many countries have reported increasing trends over recent decades. OBJECTIVE: To analyze the prevalence and trends of hypospadias for 27 international programs over a 31-yr period. DESIGN, […]
NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs
Nucleic Acids Res. 2019 Sep 19;47(16):8720-8733. doi: 10.1093/nar/gkz559. ABSTRACT Expression of human mitochondrial DNA is indispensable for proper function of the oxidative phosphorylation machinery. The mitochondrial genome encodes 22 tRNAs, 2 rRNAs and 11 mRNAs and their post-transcriptional modification constitutes one of the key regulatory steps during mitochondrial gene expression. Cytosine-5 methylation (m5C) has been […]