Molecular subtyping of tumors from patients with familial glioma
Neuro Oncol. 2018 May 18;20(6):810-817. doi: 10.1093/neuonc/nox192. ABSTRACT BACKGROUND: Single-gene mutation syndromes account for some familial glioma (FG); however, they make up only a small fraction of glioma families. Gliomas can be classified into 3 major molecular subtypes based on isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion. We hypothesized that the prevalence of molecular subtypes […]
Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects
Am J Hum Genet. 2017 Oct 5;101(4):552-563. doi: 10.1016/j.ajhg.2017.08.017. Epub 2017 Sep 28. ABSTRACT The Sonic Hedgehog (SHH) pathway is a key signaling pathway orchestrating embryonic development, mainly of the CNS and limbs. In vertebrates, SHH signaling is mediated by the primary cilium, and genetic defects affecting either SHH pathway members or ciliary proteins cause […]
Low CSF 5-HIAA in Myoclonus Dystonia
Mov Disord. 2017 Nov;32(11):1647-1649. doi: 10.1002/mds.27117. Epub 2017 Sep 26. NO ABSTRACT PMID:28949039 | PMC:PMC5796435 | DOI:10.1002/mds.27117
Homozygous Mutations in TBC1D23 Lead to a Non-degenerative Form of Pontocerebellar Hypoplasia
Am J Hum Genet. 2017 Sep 7;101(3):441-450. doi: 10.1016/j.ajhg.2017.07.015. Epub 2017 Aug 17. ABSTRACT Pontocerebellar hypoplasia (PCH) represents a group of recessive developmental disorders characterized by impaired growth of the pons and cerebellum, which frequently follows a degenerative course. Currently, there are 10 partially overlapping clinical subtypes and 13 genes known mutated in PCH. Here, […]
Should we implement population screening for fragile X?
Genet Med. 2017 Dec;19(12):1295-1299. doi: 10.1038/gim.2017.81. Epub 2017 Aug 3. NO ABSTRACT PMID:28771250 | DOI:10.1038/gim.2017.81
Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society
Genet Med. 2017 Dec;19(12):10.1038/gim.2017.107. doi: 10.1038/gim.2017.107. Epub 2017 Jul 27. ABSTRACT The purpose of this statement is to provide consensus-based recommendations for optimal management and care for patients with primary mitochondrial disease. This statement is intended for physicians who are engaged in the diagnosis and management of these patients. Working group members were appointed by […]
Analyses of SLC13A5-epilepsy patients reveal perturbations of TCA cycle.
Mol Genet Metab. 2017 Aug;121(4):314-319. doi: 10.1016/j.ymgme.2017.06.009. Epub 2017 Jun 24. PMID: 28673551; PMCID: PMC7539367. Abstract Objective: To interrogate the metabolic profile of five subjects from three families with rare, nonsense and missense mutations in SLC13A5 and Early Infantile Epileptic Encephalopathies (EIEE) characterized by severe, neonatal onset seizures, psychomotor retardation and global developmental delay. Methods: Mass spectrometry […]
A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly, epilepsy and autistic features
J Med Genet. 2018 Jan;55(1):48-54. doi: 10.1136/jmedgenet-2017-104627. Epub 2017 Jun 16. ABSTRACT BACKGROUND: Transport protein particle (TRAPP) is a multisubunit complex that regulates membrane trafficking through the Golgi apparatus. The clinical phenotype associated with mutations in various TRAPP subunits has allowed elucidation of their functions in specific tissues. The role of some subunits in human […]
Successful Application of Whole Genome Sequencing in a Medical Genetics Clinic
J Pediatr Genet. 2017 Jun;6(2):61-76. doi: 10.1055/s-0036-1593968. Epub 2016 Nov 28. ABSTRACT A pilot program was initiated using whole genome sequencing (WGS) to diagnose suspected genetic disorders in the Genetics Clinic at Children’s Hospital of Wisconsin. Twenty-two patients underwent WGS between 2010 and 2013. Initially, we obtained a 14% (3/22) diagnosis rate over 2 years; […]
Bedside Back to Bench: Building Bridges between Basic and Clinical Genomic Research
Cell. 2017 Mar 23;169(1):6-12. doi: 10.1016/j.cell.2017.03.005. ABSTRACT Genome sequencing has revolutionized the diagnosis of genetic diseases. Close collaborations between basic scientists and clinical genomicists are now needed to link genetic variants with disease causation. To facilitate such collaborations, we recommend prioritizing clinically relevant genes for functional studies, developing reference variant-phenotype databases, adopting phenotype description standards, […]