{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:45:11Z","timestamp":1777355111981,"version":"3.51.4"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2012,11,21]],"date-time":"2012-11-21T00:00:00Z","timestamp":1353456000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genet"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Severe congenital neutropenia type 4 (SCN4) is an autosomal recessive disorder caused by mutations in the third subunit of the enzyme glucose-6-phosphatase (G6PC3). Its core features are congenital neutropenia and a prominent venous skin pattern, and affected individuals have variable birth defects. Oculocutaneous albinism type 4 (OCA4) is caused by autosomal recessive mutations in <jats:italic>SLC45A2<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We report a sister and brother from Newfoundland, Canada with complex phenotypes. The sister was previously reported by Cullinane <jats:italic>et al.,<\/jats:italic> 2011. We performed homozygosity mapping, next generation sequencing and conventional Sanger sequencing to identify mutations that cause the phenotype in this family. We have also summarized clinical data from 49 previously reported SCN4 cases with overlapping phenotypes and interpret the medical histories of these siblings in the context of the literature.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The siblings\u2019 phenotype is due in part to a homozygous mutation in <jats:italic>G6PC3<\/jats:italic>, [c.829C &gt; T, p.Gln277X]. Their ages are 38 and 37\u2009years respectively and they are the oldest SCN4 patients published to date. Both presented with congenital neutropenia and later developed Crohn disease. We suggest that the latter is a previously unrecognized SCN4 manifestation and that not all affected individuals have an intellectual disability. The sister also has a homozygous mutation in <jats:italic>SLC45A2<\/jats:italic>, which explains her severe oculocutaneous hypopigmentation. Her brother carried one <jats:italic>SLC45A2<\/jats:italic> mutation and was diagnosed with \u201cpartial OCA\u201d in childhood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This family highlights that apparently novel syndromes can in fact be caused by two known autosomal recessive disorders.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2350-13-111","type":"journal-article","created":{"date-parts":[[2012,11,21]],"date-time":"2012-11-21T16:14:52Z","timestamp":1353514492000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Adult siblings with homozygous G6PC3 mutations expand our understanding of the severe congenital neutropenia type 4 (SCN4) phenotype"],"prefix":"10.1186","volume":"13","author":[{"given":"Bridget A","family":"Fernandez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane S","family":"Green","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ford","family":"Bursey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendan","family":"Barrett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9e","family":"MacMillan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"McColl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Fernandez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Proton","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krista","family":"Mahoney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio L","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen W","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kym M","family":"Boycott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael O","family":"Woods","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"FORGE Canada Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,11,21]]},"reference":[{"key":"1005_CR1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/ejhg.2010.136","volume":"19","author":"S Banka","year":"2011","unstructured":"Banka S, Chervinsky E, Newman WG, Crow YJ, Yeganeh S, Yacobovich J, Donnai D, Shalev S: Further delineation of the phenotype of severe congenital neutropenia type 4 due to mutations in G6PC3. 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