Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

The acute motor-sensory axonal neuropathy variant of Guillain-Barre syndrome after thoracic spine surgery

Guillain-Barre syndrome (GBS) is the eponym used to describe acute inflammatory polyradiculoneuropathies, which manifest with weakness and diminished reflexes. Although the classic form of GBS is considered to be an ascending demyelinating polyneuropathy, several variants have been described in the literature, including the Miller-Fisher syndrome, acute panautonomic neuropathy, acute motor axonal neuropathy, and acute motor-sensory axonal neuropathy (AMSAN). Few cases of postoperative GBS have been documented, particularly for the AMSAN variant. The authors describe the case of a patient who developed AMSAN after thoracic spine surgery and highlight the importance of investigating new-onset weakness in the postoperative period. (DOI: 10.3171/2011.8.SPINE1159

The acute motor-sensory axonal neuropathy variant of Guillain-Barré syndrome after thoracic spine surgery

Guillain-Barre syndrome (GBS) is the eponym used to describe acute inflammatory polyradiculoneuropathies, which manifest with weakness and diminished reflexes. Although the classic form of GBS is considered to be an ascending demyelinating polyneuropathy, several variants have been described in the literature, including the Miller-Fisher syndrome, acute panautonomic neuropathy, acute motor axonal neuropathy, and acute motor-sensory axonal neuropathy (AMSAN). Few cases of postoperative GBS have been documented, particularly for the AMSAN variant. The authors describe the case of a patient who developed AMSAN after thoracic spine surgery and highlight the importance of investigating new-onset weakness in the postoperative period. (DOI: 10.3171/2011.8.SPINE1159