{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:28:49Z","timestamp":1771468129228,"version":"3.50.1"},"reference-count":16,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1998,4]]},"abstract":"<jats:p>Neonatal diabetes mellitus is a rare condition, the causes of which are mostly unknown. One well defined though very rare entity is the autosomal recessive Wolcott-Rallison syndrome, in which permanent neonatal diabetes, osteopenia, and epiphyseal dysplasia occur. Only five previous families have been reported, and here we describe the second in which parental consanguinity was present. The proband was born to first cousin parents and died at 2 years from the sequelae of poorly controlled diabetes. To test the hypothesis that mutation of PAX4, required in the mouse for pancreatic islet beta cell development, might cause WRS, the structure of the human PAX4 gene was deduced and DNA from two unrelated WRS patients sequenced. No PAX4 mutation was present, though the entire coding region was sequenced in both patients. It therefore appears unlikely that PAX4 is involved in the aetiology of Wolcott-Rallison syndrome, though it remains a good candidate for other forms of neonatal diabetes mellitus.<\/jats:p>","DOI":"10.1136\/jmg.35.4.288","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"288-292","source":"Crossref","is-referenced-by-count":17,"title":["Organisation of the human PAX4 gene and its exclusion as a candidate for the Wolcott-Rallison syndrome."],"prefix":"10.1136","volume":"35","author":[{"given":"D T","family":"Bonthron","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Dunlop","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D G","family":"Barr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A A","family":"El Sanousi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L I","family":"Al-Gazali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1998,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/S0022-3476(72)80596-1","article-title":"Infancy-onset diabetes mellitus and multiple epiphyseal dysplasia","volume":"80","author":"Wolcott, C.D.; Rallison, M.L.","year":"1972","unstructured":"Wolcott CD, Rallison ML. Infancy-onset diabetes mellitus and multiple epiphyseal dysplasia. J Pediarr 1972;80:292-7.","journal-title":"J Pediarr"},{"key":"ref_2","first-page":"323","article-title":"Syndrome de transmission recessive autosomique, anociant un diabete congenital et des desordres addition to general hypoplasia of the pancreas, there was prominence of the islets and abunde la croissance des epiphyses","volume":"37","author":"P, Goumy P.Maroteaux; V, Stanescu; R, Stanescu; A, Labbe; G, Menut","year":"1980","unstructured":"Goumy P Maroteaux P, Stanescu V, Stanescu R, Labbe A, Menut G. Syndrome de transmission recessive autosomique, anociant un diabete congenital et des desordres addition to general hypoplasia of the pancreas, there was prominence of the islets and abunde la croissance des epiphyses. Arch Fr Pediatr 1980;37: 323-8.","journal-title":"Arch Fr Pediatr"},{"key":"ref_3","first-page":"120","article-title":"Wolcottdance of glucagon staining a cells, at the expense of, B cells. This is extremely similar to Rallison syndrome: diabetes mellitus and spondyloepiphyseal dysplasia","volume-title":"Eurj3Pediatr","volume":"138","author":"HJ, Stoss H.Pesech; B, Pontz; A, Otten; J, Spranger","year":"1982","unstructured":"Stoss H Pesech HJ, Pontz B, Otten A, Spranger J. Wolcottdance of glucagon staining a cells, at the expense of,B cells. This is extremely similar to Rallison syndrome: diabetes mellitus and spondyloepiphyseal dysplasia. Eurj3Pediatr 1982;138:120-9."},{"key":"ref_4","first-page":"227","article-title":"Wolcottthe histological abnormality seen in the Pax4 -\/mouse6 and prompted our analysis of PAX4 in two WRS families. Including the new family described here, two out of six reported WRS families are from the Arabian peninsula. It is possible therefore that Rallison syndrome","volume":"4","author":"Al-Gazali, L.I.; Makia, S.; Azzam, A.; Hall, C.M.","year":"1995","unstructured":"Al-Gazali LI, Makia S, Azzam A, Hall CM. Wolcottthe histological abnormality seen in the Pax4 -\/mouse6 and prompted our analysis of PAX4 in two WRS families. Including the new family described here, two out of six reported WRS families are from the Arabian peninsula. It is possible therefore that Rallison syndrome. Clin Dysmorphol 1995;4:227-33.","journal-title":"Clin Dysmorphol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/j.1399-0004.1996.tb03275.x","article-title":"Wolcott-Rallison syndrome associated with congenital malformations and a mosaic deletion 15ql1-12","volume":"49","author":"Stewart, F.J.; Carson, D.J.; Thomas, P.S.; Humphreys, M.; Thornton, M.; Nevin, N.C.","year":"1996","unstructured":"Stewart FJ, Carson DJ, Thomas PS, Humphreys M, Thornton M, Nevin NC. Wolcott-Rallison syndrome associated with congenital malformations and a mosaic deletion 15ql1-12. Clin Genet 1996;49:152-5.","journal-title":"Clin Genet"},{"key":"ref_6","article-title":"The Pax4 gene is essential for differentiation of insulinproducing I cells in the mammalian pancreas","author":"Sosa-Pineda, B.; Chowdhury, K.; Torres, M.; Oliver, G.; Gruss, P.","year":"1997","unstructured":"Sosa-Pineda B, Chowdhury K, Torres M, Oliver G, Gruss P. The Pax4 gene is essential for differentiation of insulinproducing I cells in the mammalian pancreas. Nature 1997;386:399-402. an increased frequency of WRS occurs in this ethnic group. The poor outcome in the proband is similar to that of three previous patients, and can be attributed to inadequate diabetic control with frequent swings between hypoglycaemia and ketoacidosis.","journal-title":"Nature; 386: 399-402. an increased frequency of WRS occurs in this ethnic group. The poor outcome in the proband is similar to that of three previous patients, and can be attributed to inadequate diabetic control with frequent swings between hypoglycaemia and ketoacidosis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1159\/000133684","article-title":"Assignment of the human PAX4 gene to chromosome band 7q32 by fluorescence in situ hybridization","volume":"66","author":"Tamura, T.; Izumikawa, Y.; Kishino, T.; Soejima, H.; Jinno, Y.; Niikawa, N.","year":"1994","unstructured":"Tamura T, Izumikawa Y, Kishino T, Soejima H, Jinno Y, Niikawa N. Assignment of the human PAX4 gene to chromosome band 7q32 by fluorescence in situ hybridization. Cytogenet Cell Genet 1994;66: 132-4.","journal-title":"Cytogenet Cell Genet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/0888-7543(91)90151-4","article-title":"Pax: a murine family of paired box-containing genes","volume":"11","author":"Wlather, C.; Guenet, J.L.; Simon, D.","year":"1991","unstructured":"Wlather C, Guenet JL, Simon D, et al. Pax: a murine family of paired box-containing genes. Genomics 1991; 11:424-34.","journal-title":"Genomics"},{"key":"ref_9","article-title":"Smithies 0. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res 1984; 12: 387-95. Though previous reports have emphasised MED as the major skeletal feature of","author":"Devereux, J.; Haeberli, P.","unstructured":"Devereux J, Haeberli P, Smithies 0. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res 1984;12:387-95. Though previous reports have emphasised MED as the major skeletal feature of WRS, an"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/0022-2836(91)90380-O","article-title":"Prediction of human mRNA donor and acceptor","volume":"220","author":"Brunak, S.; Engelbrecht, J.Knudsen; S.","year":"1991","unstructured":"Brunak S, Engelbrecht, J Knudsen S. Prediction of human mRNA donor and acceptor Jf Mol Biol 1991;220:49-65.","journal-title":"Jf Mol Biol"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1136\/jmg.21.4.257","article-title":"The clinical features of homozygous a2(I) collagen deficient osteogenesis imperfecta","volume":"21","author":"Nicholls, A.C.; Osse, G.; Schloon, H.G.","year":"1984","unstructured":"Nicholls AC, Osse G, Schloon HG, et al. The clinical features of homozygous a2(I) collagen deficient osteogenesis imperfecta. 7 Med Genet 1984;21:257-62.","journal-title":"7 Med Genet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1093\/hmg\/5.8.1117","article-title":"Further evidence for an imprinted gene for neonatal diabetes localised to chromosome 6q22-q23","volume":"5","author":"Temple, I.K.; Gardner, R.J.; Robinson, D.O.","year":"1996","unstructured":"Temple IK, Gardner RJ, Robinson DO, et al. Further evidence for an imprinted gene for neonatal diabetes localised to chromosome 6q22-q23. Hum Mol Genet 1996;5: 1117-21.","journal-title":"Hum Mol Genet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1172\/JCI117339","article-title":"Isodisomy of chromosome 6 in a newborn with methylmalonic acidemia and agenesis of pancreatic beta cells causing diabetes mellitus","volume":"94","author":"Abramowicz, M.J.; Andrien, M.; Dupont, E.","year":"1994","unstructured":"Abramowicz MJ, Andrien M, Dupont E, et al. Isodisomy of chromosome 6 in a newborn with methylmalonic acidemia and agenesis of pancreatic beta cells causing diabetes mellitus. Clin Invest 1994;94:418-21.","journal-title":"Clin Invest"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/371606a0","article-title":"Insulinpromoter-factor 1 is required for pancreas development in mice","volume":"371","author":"Jonsson, J.; Carlsson, L.; Edlund, T.; Edlund, H.","year":"1994","unstructured":"Jonsson J, Carlsson L, Edlund T, Edlund H. Insulinpromoter-factor 1 is required for pancreas development in mice. Nature 1994;371:606-9.","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/ng0197-106","article-title":"Pancreatic agenesis attributable to a single nucleotide deletion in the human IPFI gene coding sequence","volume":"15","author":"Stoffers, D.A.; Zinkin, N.T.; Stanojevic, V.; Clarke, W.L.; Habener, J.F.","year":"1997","unstructured":"Stoffers DA, Zinkin NT, Stanojevic V, Clarke WL, Habener JF. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPFI gene coding sequence. Nat Genet 1997;15:106-10.","journal-title":"Nat Genet"},{"key":"ref_16","first-page":"5156","article-title":"Evolution of paired domains: isolation and sequencing of jellyfish and hydra Pax genes related","volume-title":"to Pax-5 and Pax-6. Proc Nad Acad Sci","volume":"94","author":"Sun, H.; Rodin, A.; Zhou, Y.","year":"1997","unstructured":"Sun H, Rodin A, Zhou Y, et al. Evolution of paired domains: isolation and sequencing of jellyfish and hydra Pax genes related to Pax-5 and Pax-6. Proc Nad Acad Sci USA 1997; 94:5156-61."}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.35.4.288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T05:00:09Z","timestamp":1760763609000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.35.4.288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,4]]},"references-count":16,"journal-issue":{"issue":"4","published-online":{"date-parts":[[1998,4,1]]},"published-print":{"date-parts":[[1998,4]]}},"alternative-id":["10.1136\/jmg.35.4.288"],"URL":"https:\/\/doi.org\/10.1136\/jmg.35.4.288","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,4]]}}}