THURSDAY, Jan. 1 (HealthDay News) -- A gene mutation that abolishes enzyme function is associated with severe congenital neutropenia, a syndrome associated with life-threatening bacterial infections early in life, few mature neutrophils, and cardiac and urogenital abnormalities, according to a report in the Jan. 1 issue of the New England Journal of Medicine.

Kaan Boztug, M.D., from Hannover Medical School in Hannover, Germany, and colleagues performed a genome-wide screen on two unrelated families with five children affected with severe congenital neutropenia.

The researchers identified a region of chromosome 17q21 strongly associated with the syndrome. A candidate gene located in this region, glucose-6-phosphatase, catalytic subunit 3 (G6PC3) had a homozygous missense mutation that abolished the enzyme's activity in all affected children. An additional seven unrelated patients with severe congenital neutropenia also had mutations in G6PC3, the investigators found. Neutrophils and fibroblasts from these patients were more susceptible to apoptosis, and the neutrophils showed evidence of increased endoplasmic reticulum stress, the report indicates.

Noting that six genes associated with severe congenital neutropenia with differing clinical features have now been identified, the study emphasizes "the need for careful history taking and physical examination in children with severe neutropenia," David C. Dale, M.D., from the University of Washington School of Medicine in Seattle, and Daniel C. Link, M.D., from Washington University in St. Louis, write in an accompanying editorial. "Non-hematologic features may give important clues as to the correct diagnosis."

An author of the editorial has a financial relationship with the pharmaceutical industry.

Abstract
Full Text (subscription or payment may be required)
Editorial