{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:19:27Z","timestamp":1776039567215,"version":"3.50.1"},"reference-count":14,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Multiple intestinal atresia with combined immune deficiency (MIA-CID) is an autosomal recessive syndrome due to mutations in the TTC7A gene implicated in the polarization of intestinal and thymic epithelial cells. MIA-CID is lethal in the first year of life in the majority of patients. Dermatological manifestations have been reported in a few cases. We describe a child affected with MIA-CID due to a previously unreported TTC7A homozygous missense mutation. Surgery for bowel occlusion was performed in the first days of life. The patient was totally dependent on parenteral nutrition since birth and presented severe diarrhea and recurrent infections. He underwent hematopoietic stem cell transplantation at 17 months with complete donor engraftment and partial immunity improvement. In the second year of life, he progressively developed diffuse papular follicular keratoses on ichthyosiform skin, nail clubbing, and subungual hyperkeratosis. Histopathology showed hyperkeratosis with follicular plugging and scattered apoptotic keratinocytes, visualized at an ultrastructural examination. Our findings expand the spectrum of dermatological manifestations which can develop in MIA-CID patients. Examination of further patients will allow defining whether keratinocyte apoptosis is also a disease feature.<\/jats:p>","DOI":"10.3390\/genes13050821","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T08:21:25Z","timestamp":1651652485000},"page":"821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Prominent Follicular Keratosis in Multiple Intestinal Atresia with Combined Immune Deficiency Caused by a TTC7A Homozygous Mutation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0879-9825","authenticated-orcid":false,"given":"Andrea","family":"Diociaiuti","sequence":"first","affiliation":[{"name":"Dermatology Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"},{"name":"Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Caruso","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncohematology, Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6362-0667","authenticated-orcid":false,"given":"Silvia","family":"Ricci","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Health Sciences, Meyer Children\u2019s University Hospital, Viale Pieraccini 24, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"De Vito","sequence":"additional","affiliation":[{"name":"Pathology Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Strocchio","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncohematology, Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3501-6742","authenticated-orcid":false,"given":"Daniele","family":"Castiglia","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cell Biology, IDI, IRCCS, Via Monti di Creta 104, 00167 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Zambruno","sequence":"additional","affiliation":[{"name":"Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8145-4797","authenticated-orcid":false,"given":"May","family":"El Hachem","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"},{"name":"Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1136\/jmedgenet-2012-101483","article-title":"Exome sequencing identifies mutations in the gene TTC7A in French-Canadian cases with hereditary multiple intestinal atresia","volume":"50","author":"Samuels","year":"2013","journal-title":"J. Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.jaci.2013.06.013","article-title":"Whole-exome sequencing identifies tetratricopeptide repeat domain 7A (TTC7A) mutations for combined immunodeficiency with intestinal atresias","volume":"132","author":"Chen","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.jcmgh.2018.12.001","article-title":"TTC7A: Steward of intestinal health","volume":"7","author":"Jardine","year":"2019","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.3389\/fimmu.2019.02592","article-title":"Chronic intestinal pseudo-obstruction and lymphoproliferative syndrome as a novel phenotype associated with tetratricopeptide repeat domain 7A deficiency","volume":"10","author":"Lemale","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1016\/j.jaci.2014.07.019","article-title":"Immune deficiency-related enteropathy-lymphocytopenia-alopecia syndrome results from tetratricopeptide repeat domain 7A deficiency","volume":"134","author":"Lemoine","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1172\/JCI71471","article-title":"TTC7A mutations disrupt intestinal epithelial picobasal polarity","volume":"124","author":"Bigorgne","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1111\/bjd.14644","article-title":"Ichthyosis as the dermatological phenotype associated with TTC7A mutations","volume":"175","author":"Lemoine","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_8","first-page":"9","article-title":"Refractory pruritus responds to dupilumab in a patient with TTC7A mutation","volume":"8","author":"Marois","year":"2020","journal-title":"JAAD Case Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.3389\/fimmu.2017.01066","article-title":"Novel mutations of the Tetratricopeptide Repeat Domain 7A gene and phenotype\/genotype comparison","volume":"8","author":"Lien","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1053\/j.gastro.2014.01.015","article-title":"Mutations in tetratricopeptide repeat domain 7A result in a severe form of very early onset inflammatory bowel disease","volume":"146","author":"Avitzur","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"759308","DOI":"10.3389\/fimmu.2021.759308","article-title":"A novel homozygous TTC7A missense mutation results in familial multiple intestinal atresia and combined immunodeficiency","volume":"12","author":"Mou","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1182\/blood-2016-01-696385","article-title":"Stem cell transplantation for tetratricopeptide repeat domain 7A deficiency: Long-term follow-up","volume":"128","author":"Kammermeier","year":"2016","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1182\/blood-2003-04-1187","article-title":"Donor immune reconstitution after liver-small bowel transplantation for multiple intestinal atresia with immunodeficiency","volume":"103","author":"Gilroy","year":"2004","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ygeno.2004.11.008","article-title":"Positional cloning of the Ttc7 gene required for normal iron homeostasis and mutated in hea and fsn anemia mice","volume":"85","author":"White","year":"2005","journal-title":"Genomics"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/5\/821\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:06:01Z","timestamp":1760137561000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/5\/821"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,4]]},"references-count":14,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["genes13050821"],"URL":"https:\/\/doi.org\/10.3390\/genes13050821","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,4]]}}}