The p190 RhoGAPs, ARHGAP35, and ARHGAP5 are implicated in GnRH neuronal development: Evidence from patients with idiopathic hypogonadotropic hypogonadism, zebrafish, and in vitro GAP activity assay

Balasubramanian, 2011, Isolated GnRH deficiency: a disease model serving as a unique prism into the systems biology of the GnRH neuronal network, Mol Cell Endocrinol, 346, 4, 10.1016/j.mce.2011.07.012 Laitinen, 2011, Incidence, phenotypic features and molecular genetics of Kallmann syndrome in Finland, Orphanet J Rare Dis, 6, 41, 10.1186/1750-1172-6-41 Shaw ND, Brand H, Kupchinsky ZA, et al. SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome. Nat Genet. 2017;49(2):238-248. Published correction appears in Nat Genet. 2017;49(6):969. https://doi.org/10.1038/ng.3743 Davis, 2020, TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci, Hum Mol Genet, 29, 2435, 10.1093/hmg/ddaa120 Rojas, 2021, Phenotypic continuum between Waardenburg syndrome and idiopathic hypogonadotropic hypogonadism in humans with SOX10 variants, Genet Med, 23, 629, 10.1038/s41436-020-01051-3 Stamou MI, Cox KH, Crowley WF Jr. Discovering genes essential to the hypothalamic regulation of human reproduction using a human disease model: adjusting to life in the “-Omics” era. Endocr Rev. 2015;36(6):603-621. Published correction appears in Endocr Rev. 2020;41(6):886. https://doi.org/10.1210/er.2015-1045 Brouns, 2000, The adhesion signaling molecule p190 RhoGAP is required for morphogenetic processes in neural development, Development, 127, 4891, 10.1242/dev.127.22.4891 Brouns, 2001, p190 RhoGAP is the principal Src substrate in brain and regulates axon outgrowth, guidance and fasciculation, Nat Cell Biol, 3, 361, 10.1038/35070042 Matheson, 2006, Distinct but overlapping functions for the closely related p190 RhoGAPs in neural development, Dev Neurosci, 28, 538, 10.1159/000095116 Karczewski KJ, Francioli LC, Tiao G, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581(7809):434-443. Published correction appears in Nature. 2021;590(7846):E53. Published correction appears in Nature. 2021;597(7874):E3-E4. https://doi.org/10.1038/s41586-020-2308-7 Burbelo, 1995, p190-B, a new member of the Rho GAP family, and Rho are induced to cluster after integrin cross-linking, J Biol Chem, 270, 30919, 10.1074/jbc.270.52.30919 Barberis, 2005, p190 Rho-GTPase activating protein associates with plexins and it is required for semaphorin signalling, J Cell Sci, 118, 4689, 10.1242/jcs.02590 Messina, 2013, Semaphorin signaling in the development and function of the gonadotropin hormone-releasing hormone system, Front Endocrinol (Lausanne), 4, 133, 10.3389/fendo.2013.00133 Kaplanis, 2020, Evidence for 28 genetic disorders discovered by combining healthcare and research data, Nature, 586, 757, 10.1038/s41586-020-2832-5 Sobreira, 2015, GeneMatcher: a matching tool for connecting investigators with an interest in the same gene, Hum Mutat, 36, 928, 10.1002/humu.22844 Guo, 2018, Burden testing of rare variants identified through exome sequencing via publicly available control data, Am J Hum Genet, 103, 522, 10.1016/j.ajhg.2018.08.016 Adzhubei, 2013, Predicting functional effect of human missense mutations using PolyPhen-2, Curr Protoc Hum Genet, 10.1002/0471142905.hg0720s76 Choi, 2012, Predicting the functional effect of amino acid substitutions and indels, PLoS One, 7, 10.1371/journal.pone.0046688 Schwarz, 2014, MutationTaster2: mutation prediction for the deep-sequencing age, Nat Methods, 11, 361, 10.1038/nmeth.2890 Szklarczyk D, Gable AL, Nastou KC, et al. The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2021;49(D1):D605-D612. Published correction appears in Nucleic Acids Res. 2021;49(18):10800. https://doi.org/10.1093/nar/gkaa1074 Abraham, 2009, The zebrafish as a model system for forebrain GnRH neuronal development, Gen Comp Endocrinol, 164, 151, 10.1016/j.ygcen.2009.01.012 Labun, 2019, CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing, Nucleic Acids Res, 47, W171, 10.1093/nar/gkz365 Stewart, 2016, A point mutation in p190A RhoGAP affects ciliogenesis and leads to glomerulocystic kidney defects, PLoS Genet, 12, 10.1371/journal.pgen.1005785 Quinton, 1999, Kallmann’s syndrome: is it always for life?, Clin Endocrinol (Oxf), 50, 481, 10.1046/j.1365-2265.1999.00708.x Balasubramanian, 2015, Expanding the phenotypic spectrum and variability of endocrine abnormalities associated with TUBB3 E410K syndrome, J Clin Endocrinol Metab, 100, E473, 10.1210/jc.2014-4107 Latremoliere, 2018, Neuronal-specific TUBB3 is not required for normal neuronal function but is essential for timely axon regeneration, Cell Rep, 24, 1865, 10.1016/j.celrep.2018.07.029 Hanchate, 2012, SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome, PLoS Genet, 8, 10.1371/journal.pgen.1002896 Ng, 2003, SIFT: Predicting amino acid changes that affect protein function, Nucleic Acids Res, 31, 3812, 10.1093/nar/gkg509 Howard, 2016, IGSF10 mutations dysregulate gonadotropin-releasing hormone neuronal migration resulting in delayed puberty, EMBO Mol Med, 8, 626, 10.15252/emmm.201606250 Postlethwait JH, Yan YL, Gates MA, et al. Vertebrate genome evolution and the zebrafish gene map. Nat Genet. 1998;18(4):345-349. Published correction appears in Nat Genet 1998;19(3):303. https://doi.org/10.1038/ng0498-345 Borck G, Hög F, Dentici ML, et al. BRF1 mutations alter RNA polymerase III-dependent transcription and cause neurodevelopmental anomalies. Genome Res. 2015;25(2):155-166. Published correction appears in Genome Res. 2015;25(4):609. https://doi.org/10.1101/gr.176925.114 Takamiya, 2020, Pax6 organizes the anterior eye segment by guiding two distinct neural crest waves, PLoS Genet, 16, 10.1371/journal.pgen.1008774 Liu, 2011, Ccm1 regulates microvascular morphogenesis during angiogenesis, J Vasc Res, 48, 130, 10.1159/000316851 Teng, 2018, Altered bone growth dynamics prefigure craniosynostosis in a zebrafish model of Saethre-Chotzen syndrome, Elife, 7, 10.7554/eLife.37024 Kontarakis, 2020, Genetics in light of transcriptional adaptation, Trends Genet, 36, 926, 10.1016/j.tig.2020.08.008 Jenna, 2004, The superfamily of Rho GTPase-activating proteins, 68 Richards, 2015, Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, Genet Med, 17, 405, 10.1038/gim.2015.30 Héraud, 2019, p190RhoGAPs, the ARHGAP35- and ARHGAP5-encoded proteins, in health and disease, Cells, 8, 351, 10.3390/cells8040351 Miller, 2014, Data from: Transcriptional landscape of the prenatal human brain, Nature, 508, 199, 10.1038/nature13185 Lund, 2020, Characterization of the human GnRH neuron developmental transcriptome using a GNRH1-TdTomato reporter line in human pluripotent stem cells, Dis Model Mech, 13 Burger, 2018, Identification of genes enriched in GnRH neurons by translating ribosome affinity purification and RNAseq in mice, Endocrinology, 159, 1922, 10.1210/en.2018-00001 Merchenthaler, 1984, Gonadotropin-releasing hormone (GnRH) neurons and pathways in the rat brain, Cell Tissue Res, 237, 15, 10.1007/BF00229195 Siffredi, 2013, Neuropsychological profile of agenesis of the corpus callosum: a systematic review, Dev Neuropsychol, 38, 36, 10.1080/87565641.2012.721421 Ridley, 2016, Alien hand, restless brain: salience network and interhemispheric connectivity disruption parallel emergence and extinction of diagonistic dyspraxia, Front Hum Neurosci, 10, 307, 10.3389/fnhum.2016.00307 Cariboni, 2011, Defective gonadotropin-releasing hormone neuron migration in mice lacking SEMA3A signalling through NRP1 and NRP2: implications for the aetiology of hypogonadotropic hypogonadism, Hum Mol Genet, 20, 336, 10.1093/hmg/ddq468 Marcos, 2017, Defective signaling through plexin-A1 compromises the development of the peripheral olfactory system and neuroendocrine reproductive axis in mice, Hum Mol Genet, 26, 2006, 10.1093/hmg/ddx080 Kotan, 2021, Loss-of-function variants in SEMA3F and PLXNA3 encoding semaphorin-3F and its receptor plexin-A3 respectively cause idiopathic hypogonadotropic hypogonadism, Genet Med, 23, 1008, 10.1038/s41436-020-01087-5