{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T09:00:23Z","timestamp":1776589223607,"version":"3.51.2"},"reference-count":35,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T00:00:00Z","timestamp":1594166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DK105448"],"award-info":[{"award-number":["R01-DK105448"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Southwestern Medical Foundation","award":["R01-DK105448"],"award-info":[{"award-number":["R01-DK105448"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Despite considerable progress in elucidating the molecular basis of various progeroid syndromes, some rare patients remain unexplained.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To elucidate molecular genetic basis of a novel autosomal recessive progeroid syndrome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>A 24-year-old male and his 18-year-old sister with short stature, mandibular hypoplasia, pointed nose, shrill voice, severe osteoporosis, and short eyebrows and their unaffected siblings and parents belonging to a consanguineous Arab family.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Using exome and Sanger sequencing, we report a novel homozygous p.Glu394Lys disease-causing variant in proline-rich transmembrane protein 3 (PRRT3). PRRT3 belongs to the family of proline-rich proteins containing several repeats of a short proline-rich sequence, but its function remains to be determined. Preliminary observations showing colocalization of Prrt3 and synaptophysin support its role in vesicle exocytosis. Consistent with the highest messenger ribonucleic acid expression of PRRT3 in the pituitary, both the patients had mild growth hormone deficiency but had near normal reproductive development.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We conclude that the homozygous p.Glu394Lys variant in PRRT3 may be associated with a novel autosomal recessive, progeroid syndrome with short stature, mandibular hypoplasia, osteoporosis, short eyebrows, and mild growth hormone (GH) deficiency. Our findings extend the spectrum of progeroid syndromes and elucidate important functions of PRRT3 in human biology, including secretion of GH from the pituitary.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jendso\/bvaa088","type":"journal-article","created":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T13:35:31Z","timestamp":1594215331000},"source":"Crossref","is-referenced-by-count":1,"title":["A Novel Syndrome With Short Stature, Mandibular Hypoplasia, and Osteoporosis May Be Associated With a PRRT3 Variant"],"prefix":"10.1210","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7209-6986","authenticated-orcid":false,"given":"Abhimanyu","family":"Garg","sequence":"first","affiliation":[{"name":"Division of Nutrition and Metabolic Diseases, Department of Internal Medicine and the Center for Human Nutrition, UT Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hatem","family":"El-Shanti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA"},{"name":"The National Center for Diabetes, Endocrinology and Genetics, and School of Medicine, University of Jordan, Amman, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Xing","sequence":"additional","affiliation":[{"name":"McDermott Center for Human Growth and Development, Department of Population and Data Sciences, and Department of Bioinformatics, UT Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengyang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology, School of Public Health, University of North Texas Health Science Center, Fort Worth, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mousa","family":"Abujbara","sequence":"additional","affiliation":[{"name":"The National Center for Diabetes, Endocrinology and Genetics, and School of Medicine, University of Jordan, Amman, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khadeja","family":"Al-Rashed","sequence":"additional","affiliation":[{"name":"The National Center for Diabetes, Endocrinology and Genetics, and School of Medicine, University of Jordan, Amman, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"El-Khateeb","sequence":"additional","affiliation":[{"name":"The National Center for Diabetes, Endocrinology and Genetics, and School of Medicine, University of Jordan, Amman, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamel","family":"Ajlouni","sequence":"additional","affiliation":[{"name":"The National Center for Diabetes, Endocrinology and Genetics, and School of Medicine, University of Jordan, Amman, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anil K","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Division of Nutrition and Metabolic Diseases, Department of Internal Medicine and the Center for Human Nutrition, UT Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2020,7,8]]},"reference":[{"issue":"5259","key":"2020081103472464900_CIT0001","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1126\/science.272.5259.258","article-title":"Positional cloning of the Werner\u2019s syndrome gene","volume":"272","author":"Yu","year":"1996","journal-title":"Science."},{"issue":"6937","key":"2020081103472464900_CIT0002","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nature01629","article-title":"Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome","volume":"423","author":"Eriksson","year":"2003","journal-title":"Nature."},{"issue":"12","key":"2020081103472464900_CIT0003","doi-asserted-by":"crossref","first-page":"4971","DOI":"10.1210\/jc.2009-0472","article-title":"Atypical progeroid syndrome due to heterozygous missense LMNA mutations","volume":"94","author":"Garg","year":"2009","journal-title":"J Clin Endocrinol Metab."},{"issue":"2","key":"2020081103472464900_CIT0004","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1086\/341908","article-title":"Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A\/C","volume":"71","author":"Novelli","year":"2002","journal-title":"Am J Hum Genet."},{"issue":"16","key":"2020081103472464900_CIT0005","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1093\/hmg\/ddg213","article-title":"Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia","volume":"12","author":"Agarwal","year":"2003","journal-title":"Hum Mol Genet."},{"issue":"8","key":"2020081103472464900_CIT0006","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1038\/ng.2670","article-title":"An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy","volume":"45","author":"Weedon","year":"2013","journal-title":"Nat Genet."},{"issue":"6","key":"2020081103472464900_CIT0007","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.ajhg.2018.10.010","article-title":"Bi-allelic POLR3A loss-of-function variants cause autosomal-recessive Wiedemann-Rautenstrauch syndrome","volume":"103","author":"Wambach","year":"2018","journal-title":"Am J Hum Genet."},{"issue":"10","key":"2020081103472464900_CIT0008","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1210\/jc.2011-1111","article-title":"Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study","volume":"96","author":"Zemel","year":"2011","journal-title":"J Clin Endocrinol Metab."},{"issue":"9","key":"2020081103472464900_CIT0009","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"issue":"2","key":"2020081103472464900_CIT0010","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly (Austin)."},{"issue":"11","key":"2020081103472464900_CIT0011","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1093\/bioinformatics\/btw044","article-title":"BCFtools\/RoH: a hidden Markov model approach for detecting autozygosity from next-generation sequencing data","volume":"32","author":"Narasimhan","year":"2016","journal-title":"Bioinformatics."},{"issue":"12","key":"2020081103472464900_CIT0012","doi-asserted-by":"crossref","first-page":"e1001025","DOI":"10.1371\/journal.pcbi.1001025","article-title":"Identifying a high fraction of the human genome to be under selective constraint using GERP++","volume":"6","author":"Davydov","year":"2010","journal-title":"PLoS Comput Biol."},{"issue":"3","key":"2020081103472464900_CIT0013","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","author":"Kircher","year":"2014","journal-title":"Nat Genet."},{"issue":"21","key":"2020081103472464900_CIT0014","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1093\/bioinformatics\/bts526","article-title":"A robust model for read count data in exome sequencing experiments and implications for copy number variant calling","volume":"28","author":"Plagnol","year":"2012","journal-title":"Bioinformatics."},{"issue":"7","key":"2020081103472464900_CIT0015","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1242\/dmm.024711","article-title":"Hallmarks of progeroid syndromes: lessons from mice and reprogrammed cells","volume":"9","author":"Carrero","year":"2016","journal-title":"Dis Model Mech."},{"issue":"12","key":"2020081103472464900_CIT0016","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1038\/ng.1008","article-title":"Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia","volume":"43","author":"Chen","year":"2011","journal-title":"Nat Genet."},{"key":"2020081103472464900_CIT0017","author":"Garg","year":"2020"},{"issue":"10","key":"2020081103472464900_CIT0018","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.tins.2016.08.005","article-title":"PRRT2: from paroxysmal disorders to regulation of synaptic function","volume":"39","author":"Valtorta","year":"2016","journal-title":"Trends Neurosci."},{"issue":"9","key":"2020081103472464900_CIT0019","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1016\/j.celrep.2018.02.026","article-title":"SynDIG4\/Prrt1 is required for excitatory synapse development and plasticity underlying cognitive function","volume":"22","author":"Matt","year":"2018","journal-title":"Cell Rep."},{"key":"2020081103472464900_CIT0020","first-page":"S118","article-title":"Expression patterns of an orphan metabotropic receptor for Prrt3 in mice","volume":"64","author":"Yamamato","year":"2014","journal-title":"J Physiol Sci."},{"key":"2020081103472464900_CIT0021","doi-asserted-by":"crossref","first-page":"a005637","DOI":"10.1101\/cshperspect.a005637","article-title":"Synaptic vesicle exocytosis","volume":"3","author":"Sudhof","year":"2011","journal-title":"Cold Spring Harb Perspect Biol."},{"key":"2020081103472464900_CIT0022","first-page":"S118","article-title":"Comprehensive behavioral test battery analyses of the gene targeted mice of Prrt3, an orphan metabotropic receptor","volume":"64","author":"Yamamato","year":"2014","journal-title":"J Physiol Sci."},{"issue":"5","key":"2020081103472464900_CIT0023","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1210\/jcem.87.5.8509","article-title":"Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency","volume":"87","author":"Biller","year":"2002","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2020081103472464900_CIT0024","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1111\/cen.13035","article-title":"Evaluation of growth hormone stimulation testing in children","volume":"84","author":"Chesover","year":"2016","journal-title":"Clin Endocrinol (Oxf)."},{"issue":"11","key":"2020081103472464900_CIT0025","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.4158\/GL-2019-0405","article-title":"American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of growth hormone deficiency in adults and patients transitioning from pediatric to adult care","volume":"25","author":"Yuen","year":"2019","journal-title":"Endocr Pract."},{"issue":"16","key":"2020081103472464900_CIT0026","doi-asserted-by":"crossref","first-page":"6366","DOI":"10.1523\/JNEUROSCI.5126-14.2015","article-title":"Gene expression by mouse inner ear hair cells during development","volume":"35","author":"Scheffer","year":"2015","journal-title":"J Neurosci."},{"key":"2020081103472464900_CIT0027","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.arr.2016.03.002","article-title":"Werner syndrome: clinical features, pathogenesis and potential therapeutic interventions","volume":"33","author":"Oshima","year":"2017","journal-title":"Ageing Res Rev."},{"issue":"23","key":"2020081103472464900_CIT0028","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1002\/ajmg.a.31346","article-title":"Hutchinson-Gilford progeria syndrome: review of the phenotype","volume":"140","author":"Hennekam","year":"2006","journal-title":"Am J Med Genet A."},{"issue":"7","key":"2020081103472464900_CIT0029","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1002\/ajmg.a.38246","article-title":"Wiedemann-Rautenstrauch syndrome: a phenotype analysis","volume":"173","author":"Paolacci","year":"2017","journal-title":"Am J Med Genet A."},{"issue":"6","key":"2020081103472464900_CIT0030","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1210\/jc.2002-021575","article-title":"Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia-associated lipodystrophy","volume":"88","author":"Simha","year":"2003","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2020081103472464900_CIT0031","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"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","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med."},{"issue":"6","key":"2020081103472464900_CIT0032","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.ajhg.2016.04.003","article-title":"Consideration of cosegregation in the pathogenicity classification of genomic variants","volume":"98","author":"Jarvik","year":"2016","journal-title":"Am J Hum Genet."},{"issue":"6","key":"2020081103472464900_CIT0033","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.ajhg.2017.04.015","article-title":"Evaluating the clinical validity of gene-disease associations: an evidence-based framework developed by the clinical genome resource","volume":"100","author":"Strande","year":"2017","journal-title":"Am J Hum Genet."},{"issue":"10","key":"2020081103472464900_CIT0034","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/humu.22844","article-title":"GeneMatcher: a matching tool for connecting investigators with an interest in the same gene","volume":"36","author":"Sobreira","year":"2015","journal-title":"Hum Mutat."},{"issue":"12","key":"2020081103472464900_CIT0035","doi-asserted-by":"crossref","first-page":"6111","DOI":"10.1074\/jbc.M115.683888","article-title":"A novel topology of proline-rich transmembrane protein 2 (PRRT2): hints for an intracellular function at the synapse","volume":"291","author":"Rossi","year":"2016","journal-title":"J Biol Chem."}],"container-title":["Journal of the Endocrine Society"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jes\/advance-article-pdf\/doi\/10.1210\/jendso\/bvaa088\/33474656\/bvaa088.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jes\/article-pdf\/4\/8\/bvaa088\/33638073\/bvaa088.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jes\/article-pdf\/4\/8\/bvaa088\/33638073\/bvaa088.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T07:55:12Z","timestamp":1597132512000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jes\/article\/doi\/10.1210\/jendso\/bvaa088\/5868816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,8]]},"references-count":35,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jendso\/bvaa088","relation":{},"ISSN":["2472-1972"],"issn-type":[{"value":"2472-1972","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,8]]},"published":{"date-parts":[[2020,7,8]]},"article-number":"bvaa088"}}