Archives: RSS Publications

Bi-allelic loss-of-function variants in TMEM147 cause moderate to profound intellectual disability with facial dysmorphism and pseudo-Pelger-Huët anomaly

Am J Hum Genet. 2022 Aug 23:S0002-9297(22)00360-3. doi: 10.1016/j.ajhg.2022.08.008. Online ahead of print. ABSTRACT The transmembrane protein TMEM147 has a dual function: first at the nuclear envelope, where it anchors lamin B receptor (LBR) to the inner membrane, and second at the endoplasmic reticulum (ER), where it facilitates the translation of nascent polypeptides within the […]

Subgroup-Enriched Pathways and Kinase Signatures in Medulloblastoma Patient-Derived Xenografts

J Proteome Res. 2022 Aug 17. doi: 10.1021/acs.jproteome.2c00203. Online ahead of print. ABSTRACT Medulloblastoma (MB) is the most common malignant pediatric brain tumor. MB is classified into four primary molecular subgroups: wingless (WNT), sonic hedgehog (SHH), Group 3 (G3), and Group 4 (G4), and further genomic and proteomic subtypes have been reported. Subgroup heterogeneity and […]

The long non-coding RNA SPRIGHTLY and its binding partner PTBP1 regulate exon 5 skipping of SMYD3 transcripts in group 4 medulloblastomas

Neurooncol Adv. 2022 Aug 2;4(1):vdac120. doi: 10.1093/noajnl/vdac120. eCollection 2022 Jan-Dec. ABSTRACT BACKGROUND: Although some of the regulatory genes, signaling pathways, and gene regulatory networks altered in medulloblastomas (MB) are known, the roles of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), are poorly described. Here we report that the lncRNA SPRIGHTLY (SPRY4-IT1) gene is upregulated in […]

De Novo ZMYND8 variants result in an autosomal dominant neurodevelopmental disorder with cardiac malformations

Genet Med. 2022 Aug 1:S1098-3600(22)00803-6. doi: 10.1016/j.gim.2022.06.001. Online ahead of print. ABSTRACT PURPOSE: ZMYND8 encodes a multidomain protein that serves as a central interactive hub for coordinating critical roles in transcription regulation, chromatin remodeling, regulation of super-enhancers, DNA damage response and tumor suppression. We delineate a novel neurocognitive disorder caused by variants in the ZMYND8 […]

Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability

Science. 2022 Jul 29;377(6605):511-517. doi: 10.1126/science.abm6222. Epub 2022 Jul 28. ABSTRACT We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of […]

An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases

Nat Commun. 2022 Jul 26;13(1):4057. doi: 10.1038/s41467-022-31446-6. While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for […]

Combined MEK and JAK/STAT3 pathway inhibition effectively decreases SHH medulloblastoma tumor progression

Commun Biol. 2022 Jul 14;5(1):697. doi: 10.1038/s42003-022-03654-9. ABSTRACT Medulloblastoma (MB) is the most common primary malignant pediatric brain cancer. We recently identified novel roles for the MEK/MAPK pathway in regulating human Sonic Hedgehog (SHH) MB tumorigenesis. The MEK inhibitor, selumetinib, decreased SHH MB growth while extending survival in mouse models. However, the treated mice ultimately […]

Bi-allelic loss-of-function variants in PPFIBP1 cause a neurodevelopmental disorder with microcephaly, epilepsy, and periventricular calcifications

Am J Hum Genet. 2022 Jul 7:S0002-9297(22)00261-0. doi: 10.1016/j.ajhg.2022.06.008. Online ahead of print. ABSTRACT PPFIBP1 encodes for the liprin-β1 protein, which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome and genome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 16 individuals from 12 unrelated […]

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