{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T05:10:36Z","timestamp":1775279436951,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Trichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder of DNA repair and transcription with developmental delay and abnormalities in brain, eye, skin, nervous, and musculoskeletal systems. We followed a cohort of 37 patients with TTD at the National Institutes of Health (NIH) from 2001 to 2019 with a median age at last observation of 12\u2009years (range 2\u201336). Some children with TTD developed rapidly debilitating hip degeneration (DHD): a distinctive pattern of hip pain, inability to walk, and avascular necrosis on imaging. Ten (27%) of the 37 patients had DHD at median age 8\u2009years (range 5\u201312), followed by onset of imaging findings at median age 9\u2009years (range 5\u201313). All 10 had mutations in the <jats:italic>ERCC2<\/jats:italic>\/<jats:italic>XPD<\/jats:italic> gene. In 7 of the 10 affected patients, DHD rapidly became bilateral. DHD was associated with coxa valga, central osteosclerosis with peripheral osteopenia of the skeleton, and contractures\/tightness of the lower limbs. Except for one patient, surgical interventions were generally not effective at preventing DHD. Four patients with DHD died at a median age of 11\u2009years (range 9\u201315). TTD patients with <jats:italic>ERCC2<\/jats:italic>\/<jats:italic>XPD<\/jats:italic> gene mutations have a high risk of musculoskeletal abnormalities and DHD leading to poor outcomes. Monitoring by history, physical examination, imaging, and by physical medicine and rehabilitation specialists may be warranted.<\/jats:p>","DOI":"10.1002\/ajmg.a.62962","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T15:15:41Z","timestamp":1663168541000},"page":"3448-3462","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Debilitating hip degeneration in trichothiodystrophy: Association with <scp><i>ERCC2<\/i><\/scp>\/<scp><i>XPD<\/i><\/scp> mutations, osteosclerosis, osteopenia, coxa valga, contractures, and osteonecrosis"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2750-2313","authenticated-orcid":false,"given":"John J.","family":"DiGiovanna","sequence":"first","affiliation":[{"name":"DNA Repair Section Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grant","family":"Randall","sequence":"additional","affiliation":[{"name":"DNA Repair Section Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH  Bethesda Maryland USA"},{"name":"NIH Medical Research Scholars Program  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Edelman","sequence":"additional","affiliation":[{"name":"DNA Repair Section Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rina","family":"Allawh","sequence":"additional","affiliation":[{"name":"DNA Repair Section Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Xiong","sequence":"additional","affiliation":[{"name":"DNA Repair Section Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4812-5622","authenticated-orcid":false,"given":"Deborah","family":"Tamura","sequence":"additional","affiliation":[{"name":"DNA Repair Section Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9957-4132","authenticated-orcid":false,"given":"Sikandar G.","family":"Khan","sequence":"additional","affiliation":[{"name":"DNA Repair Section Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3833-890X","authenticated-orcid":false,"given":"Elizabeth R. H.","family":"Rizza","sequence":"additional","affiliation":[{"name":"DNA Repair Section Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James C.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging Sciences Clinical Center, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott M.","family":"Paul","sequence":"additional","affiliation":[{"name":"Rehabilitation Medicine Department Clinical Center, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suvimol C.","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Radiology Clinical Center, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2689-3316","authenticated-orcid":false,"given":"Kenneth H.","family":"Kraemer","sequence":"additional","affiliation":[{"name":"DNA Repair Section Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1416181112"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19051407"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000000458"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/BPB.0b013e32832f5aeb"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab123"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20768"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2011.05.036"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650040611"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102418"},{"key":"e_1_2_5_11_1","volume-title":"2019 International Society for Clinical Densitometry Official Positions","author":"Densitometry TISFC","year":"2019"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.426"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.058743"},{"key":"e_1_2_5_14_1","volume-title":"Osteonecrosis of the hip. OrthoInfo","author":"Foran J. R. H.","year":"2018"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1665"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.440"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000079272.91782.b1"},{"key":"e_1_2_5_18_1","volume-title":"Hip osteonecrosis","author":"Hsu H.","year":"2022"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-008-0062-1"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/BPO.0b013e318223b423"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.12.020"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.01.006"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.02.008"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-004-1323-4"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2006.01.025"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2004.09.013"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700384"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01336.x"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds508"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ocl.2011.03.002"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.90"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.2829"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.06.017"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-004-1207-7"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1385\/JCD:8:1:001"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2010.03.041"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.246"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62962","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62962","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62962","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T13:05:16Z","timestamp":1692536716000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,14]]},"references-count":36,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/ajmg.a.62962"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62962","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,14]]},"assertion":[{"value":"2022-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}