{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:58:52Z","timestamp":1791417532910,"version":"4.3.3"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,1,3]],"date-time":"2017-01-03T00:00:00Z","timestamp":1483401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005402","name":"Dasman Diabetes Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005402","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To characterize the underlying genetic and molecular defects in a consanguineous family with lifelong blood disorder manifested with thrombocytopenia (low platelets count) and anemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genetic linkage analysis, exome sequencing, and functional genomics were carried out to identify and characterize the defective gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a novel truncation mutation (p.C108*) in chromosome 6 open reading frame 25 (<jats:italic>C6orf25<\/jats:italic>) gene in this family. We also showed the p.C108* mutation was responsible for destabilizing the encoded truncated G6B protein. Unlike the truncated form, wild\u2010type G6B expression resulted in enhanced K562 differentiation into megakaryocytes and erythrocytes. C6orf25, also known as <jats:italic>G6B<\/jats:italic>, is an effector protein for the key hematopoiesis regulators, Src homology region 2 domain\u2010containing phosphatases <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content>\u20101 and <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content>\u20102.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>G6B<\/jats:italic> seems to act through an autosomal recessive mode of disease transmission in this family and regarded as the gene responsible for the observed hematological disorder. This inference is well supported further by <jats:italic>in vivo<\/jats:italic> evidence where similar outcomes were reported from G6b<jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content>1\/2 <jats:styled-content style=\"fixed-case\">DKO<\/jats:styled-content> mouse models.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.12819","type":"journal-article","created":{"date-parts":[[2016,10,15]],"date-time":"2016-10-15T07:06:39Z","timestamp":1476515199000},"page":"218-227","source":"Crossref","is-referenced-by-count":38,"title":["Novel G6B gene variant causes familial autosomal recessive thrombocytopenia and anemia"],"prefix":"10.1111","volume":"98","author":[{"given":"Motasem","family":"Melhem","sequence":"first","affiliation":[{"name":"Genetics and Genomics Department Dasman Diabetes Institute Dasman 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