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HSAN2B is characterized by sensory impairment resulting in skin ulcerations, amputations, and osteomyelitis as well as variable weakness, spasticity, and autonomic dysfunction. Here, we report four affected individuals with recurrent osteomyelitis, ulceration, and amputation of hands and feet, sensory neuropathy, hyperhidrosis, urinary incontinence, and renal failure from a family without any known shared parental ancestry. Due to the history of chronic recurrent multifocal osteomyelitis and microcytic anemia, a diagnosis of Majeed syndrome was considered; however, sequencing of <jats:italic>LPIN2<\/jats:italic> was negative. Family\u2010based exome sequencing (ES) revealed a novel homozygous ultrarare <jats:italic>RETREG1<\/jats:italic> variant NM_001034850.2:c.321G&gt;A;p.Trp107Ter. Electrophysiological studies of the proband demonstrated axonal sensorimotor neuropathy predominantly in the lower extremities. Consistent with the lack of shared ancestry, the coefficient of inbreeding calculated from ES data was low (<jats:italic>F<\/jats:italic>\u00a0=\u00a00.002), but absence of heterozygosity (AOH) analysis demonstrated a 7.2\u00a0Mb AOH block surrounding the variant consistent with a founder allele. Two of the four affected individuals had unexplained renal failure which has not been reported in HSAN2B cases to date. Therefore, this report describes a novel <jats:italic>RETREG1<\/jats:italic> founder allele and suggests renal failure may be an unrecognized feature of the <jats:italic>RETREG1<\/jats:italic>\u2010disease spectrum.<\/jats:p>","DOI":"10.1002\/ajmg.a.62727","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T05:17:45Z","timestamp":1648185465000},"page":"2153-2161","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel <i>RETREG1<\/i> (<scp><i>FAM134B)<\/i><\/scp> founder allele is linked to <scp>HSAN2B<\/scp> and renal disease in a Turkish family"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3917-9792","authenticated-orcid":false,"given":"Elifcan","family":"Ta\u015fdelen","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Sanliurfa Education and Research Hospital  \u015eanl\u0131urfa Turkey"},{"name":"Department of Medical Genetics Ankara University School of Medicine  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6860-372X","authenticated-orcid":false,"given":"Daniel G.","family":"Calame","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulsen","family":"Akay","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Department of Pediatrics University of Utah  Salt Lake Utah 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National Research Hospital  Boys Town Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowei","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep","family":"Coban\u2010Akdemir","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, Human Genetics Center The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Marafi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Department of Pediatrics, Faculty of Medicine Kuwait University  Safat Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini N.","family":"Jhangiani","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4814-6765","authenticated-orcid":false,"given":"Jennifer E.","family":"Posey","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1356-5698","authenticated-orcid":false,"given":"Richard A.","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Human Genome Sequencing Center Baylor College of Medicine  Houston Texas 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of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5788-0270","authenticated-orcid":false,"given":"Davut","family":"Pehlivan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas 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I.(1993).Hereditary sensory and autonomic neuropathy type II. InM. P.Adam H. H.Ardinger R. A.Pagon S. E.Wallace B.LJH G.Mirzaa &A.Amemiya(Eds.).GeneReviews([R])."},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.464"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200600"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.09.008"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2010.228965"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1973.00490250041005"},{"issue":"1085","key":"e_1_2_7_18_1","article-title":"Hereditary sensory and autonomic neuropathy 2B caused by a novel RETREG1 mutation (c.765dupT) and paternal uniparental isodisomy of chromosome 5","volume":"10","author":"Park G. 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