Genetic analysis and clinical picture of severe congenital neutropenia in Israel. Issue 1 (4th October 2014)

• Record Type: Journal Article
• Authors: Lebel, Asaf; Yacobovich, Joanne; Krasnov, Tanya; Koren, Ariel; Levin, Carina; Kaplinsky, Chaim; Ravel‐Vilk, Shoshana; Laor, Ruth; Attias, Dina; Barak, Ayelet Ben; Shtager, Dalia; Stein, Jerry; Kuperman, Amir; Miskin, Hagit; Dgany, Orly; Giri, Neelam; Alter, Blanche P.; Tamary, Hannah
• Is Part Of: Pediatric blood & cancer. Volume 62:Issue 1(2015:Jan.)
• Page Start: 103
• Page End: 108
• Publication Date: 2014-10-04
• Subjects: Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.25251
• Languages: English
• ISSNs: 1545-5009

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pbc25251-sec-0001" sec-type="section"> <title>Background</title> <p>The relative frequency of mutated genes among patients with severe congenital neutropenia (SCN) may differ between various ethnic groups. To date, few population‐based genetic studies have been reported. This study describes the genetic analysis of 32 Israeli patients with SCN.</p> </sec> <sec id="pbc25251-sec-0002" sec-type="section"> <title>Procedures</title> <p>Clinical data were retrieved from the prospective Israeli Inherited Bone Marrow Failure Registry. Recruitment included living and deceased patients who were diagnosed between 1982 and 2012, for whom molecular diagnosis was performed. <italic>ELANE</italic>, <italic>HAX1</italic> and <italic>G6PC3</italic> genes were sequenced in all patients, and <italic>GFI‐1</italic> and <italic>WAS</italic> genes were sequenced if other genes were wildtype.</p> </sec> <sec id="pbc25251-sec-0003" sec-type="section"> <title>Results</title> <p>Eleven patients (34%) had heterozygous mutations in <italic>ELANE</italic> (10 kindreds), eight (25%) had homozygous mutations in <italic>G6PC3</italic> (5 kindreds) and 13 (41%) had no detected mutations. No patients had mutations in <italic>HAX1</italic> or <italic>WAS</italic>. Four of the eight patients with <italic>G6PC3</italic> mutations had congenital anomalies. The probability of survival for all patients was 50% at age of 18. Deaths were mainly due to sepsis (5 patients, 4/5 not responding to G‐CSF, none with <italic>G6PC3</italic> mutation). Two patients developed acute myelogenous leukemia (AML) and one myelodysplastic syndrome (MDS), none with <italic>G6PC3</italic> mutation.</p> </sec> <sec id="pbc25251-sec-0004" sec-type="section"> <title>Conclusions</title> <p>We found a unique pattern of SCN mutations in Israel with homozygous <italic>G6PC3</italic> mutations in eight (25%) patients, the highest frequency described so far. <italic>HAX1</italic> mutations, reported mainly in Sweden and Iran, were absent. Patients with <italic>G6PC3</italic> mutations had congenital anomalies, appeared to have a better response to G‐CSF, and so far have not developed AML or MDS. Pediatr Blood Cancer 2015;62:103–108. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>