Partially automated whole-genome sequencing reanalysis of previously undiagnosed pediatric patients can efficiently yield new diagnoses
NPJ Genom Med. 2020 Aug 11;5:33. doi: 10.1038/s41525-020-00140-1. eCollection 2020. ABSTRACT To investigate the diagnostic and clinical utility of a partially automated reanalysis pipeline, forty-eight cases of seriously ill children with suspected genetic disease who did not receive a diagnosis upon initial manual analysis of whole-genome sequencing (WGS) were reanalyzed at least 1 year later. […]
Loss of NARS1 impairs progenitor proliferation in cortical brain organoids and leads to microcephaly
Nat Commun. 2020 Aug 12;11(1):4038. doi: 10.1038/s41467-020-17454-4. ABSTRACT Asparaginyl-tRNA synthetase1 (NARS1) is a member of the ubiquitously expressed cytoplasmic Class IIa family of tRNA synthetases required for protein translation. Here, we identify biallelic missense and frameshift mutations in NARS1 in seven patients from three unrelated families with microcephaly and neurodevelopmental delay. Patient cells show reduced […]
Biallelic loss of function variants in SYT2 cause a treatable congenital onset presynaptic myasthenic syndrome
Am J Med Genet A. 2020 Oct;182(10):2272-2283. doi: 10.1002/ajmg.a.61765. Epub 2020 Aug 10. ABSTRACT Synaptotagmins are integral synaptic vesicle membrane proteins that function as calcium sensors and regulate neurotransmitter release at the presynaptic nerve terminal. Synaptotagmin-2 (SYT2), is the major isoform expressed at the neuromuscular junction. Recently, dominant missense variants in SYT2 have been reported […]
Correction to: Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies
Orphanet J Rare Dis. 2020 Aug 5;15(1):202. doi: 10.1186/s13023-020-01464-y. ABSTRACT An amendment to this paper has been published and can be accessed via the original article. PMID:32758270 | PMC:PMC7409715 | DOI:10.1186/s13023-020-01464-y
Clinician-centric diagnosis of rare genetic diseases: performance of a gene pertinence metric in decision support for clinicians
Orphanet J Rare Dis. 2020 Jul 22;15(1):191. doi: 10.1186/s13023-020-01461-1. ABSTRACT BACKGROUND: In diagnosis of rare genetic diseases we face a decision as to the degree to which the sequencing lab offers one or more diagnoses based on clinical input provided by the clinician, or the clinician reaches a diagnosis based on the complete set of […]
Pathogenic ARH3 mutations result in ADP-ribose chromatin scars during DNA strand break repair
Nat Commun. 2020 Jul 7;11(1):3391. doi: 10.1038/s41467-020-17069-9. ABSTRACT Neurodegeneration is a common hallmark of individuals with hereditary defects in DNA single-strand break repair; a process regulated by poly(ADP-ribose) metabolism. Recently, mutations in the ARH3 (ADPRHL2) hydrolase that removes ADP-ribose from proteins have been associated with neurodegenerative disease. Here, we show that ARH3-mutated patient cells accumulate […]
Diagnosis of cytomegalovirus infection from clinical whole genome sequencing
Sci Rep. 2020 Jul 3;10(1):11020. doi: 10.1038/s41598-020-67656-5. ABSTRACT Rapid whole genome sequencing (rWGS) of peripheral blood has been used to detect microbial DNA in acute infections. Cytomegalovirus (CMV) is a herpesvirus capable of causing severe disease in neonates and immunocompromised patients. We identified CMV in patients undergoing diagnostic rWGS by matching reads that did not […]
Commentary
Clin Chem. 2020 Jan 1;66(1):51-52. doi: 10.1093/clinchem.2019.310037. Comment on Unconventional Diagnosis Based on Somatic Findings through Germ Line Whole-Exome Sequencing. Lopes JL, Rasmussen KJ, Mehta N, Boczek NJ, Hasadsri L.Clin Chem. 2020 Jan 1;66(1):48-51. doi: 10.1093/clinchem.2019.304451.PMID: 32609848 PMID:32609850 | DOI:10.1093/clinchem.2019.310037
Adaptive functioning in children and adolescents with Trisomy X: An exploratory analysis
Am J Med Genet C Semin Med Genet. 2020 Jun;184(2):456-468. doi: 10.1002/ajmg.c.31803. Epub 2020 Jun 17. ABSTRACT Identifying the factors related to adaptive functioning will improve the information available to families and providers of females with Trisomy X. Cognitive and behavioral features were assessed in 50 females ages 12.2 ± 3.6 years using the Behavior […]
Failure to thrive – an overlooked manifestation of KMT2B-related dystonia: a case presentation
BMC Neurol. 2020 Jun 16;20(1):246. doi: 10.1186/s12883-020-01798-x. ABSTRACT BACKGROUND: KMT2B-related dystonia is a recently described form of childhood onset dystonia that may improve with deep brain stimulation. Prior reports have focused on neurologic features including prominent bulbar involvement without detailing general health consequences that may result from orolingual dysfunction. We describe a family with novel […]