{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T14:49:15Z","timestamp":1763563755643},"reference-count":24,"publisher":"Wiley","issue":"S3","license":[{"start":{"date-parts":[[2010,7,6]],"date-time":"2010-07-06T00:00:00Z","timestamp":1278374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Transcobalamin (TC) deficiency (OMIM# 275350) is a rare, autosomal recessive disorder that presents in early infancy with a broad spectrum of symptoms, including failure to thrive, megaloblastic anemia, immunological deficiency, and neurological symptoms. Here we report a study of a family (parents and three children) with two children suffering from TC deficiency caused by two different mutations in the <jats:italic>TCN2<\/jats:italic> gene. Initially, molecular genetic analysis of genomic DNA revealed a heterozygous mutation in the +1 position of exon 7 (c.1106+1 G &gt; A) in the father and all three children. Bioinformatic analysis indicates that this mutation causes exon skipping, and further experiments supported this hypothesis and suggested that the mutant allele undergoes nonsense\u2010mediated messenger RNA (mRNA) decay. We did not identify further mutations in genomic DNA that could explain TC deficiency in the two children. However, further efforts using complementary DNA (cDNA) derived from RNA from blood leukocytes identified a large deletion removing the entire exon 8, resulting in a frameshift and a premature stop codon (p.E371fsX372) in the mother and the two affected children. Our data indicate that if exon\u2010by\u2010exon DNA sequencing of genomic DNA does not uncover mutations corresponding to the phenotype, a systematic search for other mutations should be initiated by sequencing cDNA or using semiquantitative methods to detect large deletions in <jats:italic>TCN2<\/jats:italic>.<\/jats:p>","DOI":"10.1007\/s10545-010-9145-z","type":"journal-article","created":{"date-parts":[[2010,7,5]],"date-time":"2010-07-05T08:22:37Z","timestamp":1278318157000},"page":"269-274","source":"Crossref","is-referenced-by-count":13,"title":["Transcobalamin deficiency caused by compound heterozygosity for two novel mutations in the <i>TCN2<\/i> gene: a study of two affected siblings, their brother, and their parents"],"prefix":"10.1002","volume":"33","author":[{"given":"Peter H.","family":"Nissen","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, AS Aarhus University Hospital Norrebrogade 44 Aarhus C DK 8000 Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Nordwall","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vrinnevi Hospital, Norrk\u00f6ping and Division of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke","family":"Hoffmann\u2010L\u00fccke","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, AS Aarhus University Hospital Norrebrogade 44 Aarhus C DK 8000 Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boe S.","family":"Sorensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, AS Aarhus University Hospital Norrebrogade 44 Aarhus C DK 8000 Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebba","family":"Nexo","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, AS Aarhus University Hospital Norrebrogade 44 Aarhus C DK 8000 Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,7,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nu.07.070187.001451"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21137"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2009.34"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2003.028472"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1566807"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201649"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00210743"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.10.1835"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2577"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccn.2005.01.013"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04685.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/9783527612192.ch30"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/46.10.1643"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/48.3.561"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2005.057810"},{"key":"e_1_2_6_17_1","unstructured":"PrasadC RosenblattDS CorleyK CairneyAE RuparCA(2008)Transcobalamin (TC) deficiency\u2010potential cause of bone marrow failure in childhood.J Inherit Metab Disdoi:10.1007\/s10545\u2010008\u20100864\u20103"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/bcmd.2002.0499"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/35.2.260"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.06.003"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.1997.4.311"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.10.2711.bloodjournal85102711"},{"key":"e_1_2_6_23_1","first-page":"3897","volume-title":"The metabolic and molecular bases of inherited disease","author":"Rosenblatt 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