eprintid: 10075954 rev_number: 28 eprint_status: archive userid: 608 dir: disk0/10/07/59/54 datestamp: 2019-06-14 14:46:28 lastmod: 2021-12-13 03:11:01 status_changed: 2019-06-14 14:46:28 type: article metadata_visibility: show creators_name: Riachi, M creators_name: Bas, F creators_name: Darendeliler, F creators_name: Hussain, K title: A novel 3' untranslated region mutation in the SLC29A3 gene associated with pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus syndrome ispublished: pub divisions: UCL divisions: B02 divisions: D13 divisions: G23 keywords: Science & Technology, Life Sciences & Biomedicine, Endocrinology & Metabolism, Pediatrics, 3 ' untranslated region (3 ' UTR), diabetes mellitus (DM), hyperpigmentation, messenger RNA (mRNA), PHID syndrome, NUCLEOSIDE TRANSPORTER FAMILY, H SYNDROME, IDENTIFICATION, RNA note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: Background Pigmentary hypertrichosis and non‐autoimmune insulin‐dependent diabetes mellitus (PHID) is one of the rare H syndrome diseases mainly characterized by hyperpigmentation, hypertrichosis, sensorineural hearing loss, cardiac complications, developmental delay, and diabetes mellitus (DM). Mutations in the coding regions of the SLC29A3 gene that encodes for an equilibrative nucleoside transporter (ENT3) have been reported to cause the phenotypic spectrum of the H syndrome. Disease‐causing mutations in the untranslated regions (UTRs) of the SLC29A3 gene have not been previously described in the literature. The aim of the study is to describe and assess the pathogenicity of a novel 3’UTR mutation in the SLC29A3 gene associated with the PHID phenotype in two Turkish patients. Methods The mutation was identified by a targeted gene approach. To understand the pathogenicity of this 3’UTR mutation, RNA and protein expression studies were performed by using the quantitative real‐time polymerase chain reaction method and western blotting, respectively, using fibroblasts cultured from the patients' skin biopsies. Results SLC29A3 and ENT3 expression levels were both decreased in the patients compared to controls matched for passage numbers, RNA, and protein extraction methods. Conclusions A novel 3’UTR mutation in the SLC29A3 gene is associated with the PHID syndrome, highlighting a potentially new pathological mechanism for this disease. The involvement of the 3’UTR has not been previously established in any of the H syndrome disease cluster or in any complex syndrome of DM. date: 2019-06 date_type: published publisher: WILEY official_url: https://doi.org/10.1111/pedi.12839 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Article verified: verified_manual elements_id: 1638138 doi: 10.1111/pedi.12839 lyricists_name: Hussain, Khalid lyricists_name: Riachi, Melissa lyricists_id: KHUSS37 lyricists_id: MRIAC58 actors_name: Riachi, Melissa actors_id: MRIAC58 actors_role: owner full_text_status: public publication: Pediatric Diabetes volume: 20 number: 4 pagerange: 474-481 pages: 8 issn: 1399-5448 citation: Riachi, M; Bas, F; Darendeliler, F; Hussain, K; (2019) A novel 3' untranslated region mutation in the SLC29A3 gene associated with pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus syndrome. Pediatric Diabetes , 20 (4) pp. 474-481. 10.1111/pedi.12839 <https://doi.org/10.1111/pedi.12839>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10075954/3/Riachi%20-%20UCL%20RPS.pdf