{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:17:06Z","timestamp":1784888226253,"version":"3.55.0"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,9,10]],"date-time":"2017-09-10T00:00:00Z","timestamp":1505001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Triphalangeal thumbs (TPTs) are regularly caused by mutations in the ZRS in <jats:italic>LMBR1<\/jats:italic>. Phenotypic variability can be present in TPT\u2010families. However, recent observations suggest an increased occurrence of severe phenotypes in the Dutch TPT\u2010population. Therefore, the aim of this study is to investigate the progression of the clinical severity of TPT\u2010phenotype through generations. Index patients from a Dutch TPT\u2010population were identified. A 105C&gt;G mutation in the ZRS has previously been confirmed in this population. Questionnaires regarding family occurrence and phenotypes were distributed. Subsequently, families were visited to validate the phenotype. Both occurrence and inheritance patterns of the TPT\u2010phenotype were analyzed through multiple generations. One hundred seventy patients with TPT were identified from 11 families. When considering all 132 segregations (parent\u2010to\u2010child transmission), 54% of the segregations produced a stable phenotype, 38% produced a more severe phenotype while only 8% of the phenotype was less severe when compared to the affected parents. Overall, 71% of the index patients had a more severe phenotype compared to their great\u2010grandparent. Although all family members share an identical mutation in the ZRS (105C&gt;G), it does not explain the wide phenotypic range of anomalies. Our observational study provides better estimations for counseling and provides new insights in the long\u2010range regulation of SHH by the ZRS\u2010enhancer. In the current study, we provide evidence that the assumed variability in TPT\u2010phenotype is not random, but in fact it is more likely that the expression becomes more severe in the next generation. Therefore, we observe a pattern that resembles phenotypic anticipation in TPT\u2010families.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38398","type":"journal-article","created":{"date-parts":[[2017,9,10]],"date-time":"2017-09-10T09:46:39Z","timestamp":1505036799000},"page":"2898-2905","source":"Crossref","is-referenced-by-count":10,"title":["Intrafamilial variability of the triphalangeal thumb phenotype in a Dutch population: Evidence for phenotypic progression over generations?"],"prefix":"10.1002","volume":"173","author":[{"given":"Martijn","family":"Baas","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery and Hand Surgery Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4893-3064","authenticated-orcid":false,"given":"Jacob W.P.","family":"Potuijt","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery and Hand Surgery Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.R.","family":"Hovius","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery and Hand Surgery Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Jeannette M.","family":"Hoogeboom","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert\u2010Jan H.","family":"Galjaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christianne A.","family":"van Nieuwenhoven","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery and Hand Surgery Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753193413479263"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.127"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19991222)87:5<399::AID-AJMG6>3.0.CO;2-A"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912818107"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.225"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn141"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.14.7458"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/302961"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31563"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1999.5796"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0394-287"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.112212199"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg180"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5261.548"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0363-5023(88)80019-4"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.25.8.505"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.113"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22581"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12534"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21142"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5193(69)80016-0"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.6.462"},{"key":"e_1_2_7_24_1","first-page":"32","article-title":"Clinical and genetic studies on 12 preaxial polydactyly families and refinement of the localisation of the gene responsible to a 1.9 cM region on chromosome 7q36","volume":"36","author":"Zguricas J.","year":"1999","journal-title":"Journal of Medical Genetics"},{"key":"e_1_2_7_25_1","first-page":"281","article-title":"[ZRS mutations in two Chinese Han families featuring triphalangeal thumbs and preaxial polydactyly]","volume":"33","author":"Zhao X.","year":"2016","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ede.0000152526.63279.da"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.38398","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38398","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T06:17:16Z","timestamp":1696573036000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38398"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,10]]},"references-count":25,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1002\/ajmg.a.38398"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38398","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,10]]}}}