A new exon 9 glucose-6-phosphate dehydrogenase mutation (G6PD "Rehovot") in a Jewish Ethiopian family with variable phenotypes

Hereditary nonspherocytic hemolytic anemia (HNSHA) is a rare manifestation of glucose-6-phosphate dehydrogenase (G6PD) gene mutations, caused mainly b y mutations located in exon 10 of the G6PD gene and less commonly by mutati ons in other parts of the gene. A new, exon 9, single-base mutation represe nting a T --> C transition at cDNA nucleotide 964 was found in three brothe rs and their carrier mother of Jewish Ethiopian descent. Biochemical charac terization of the resultant protein was not performed. Though clinical mani festations included HNSHA in all cases, the severity of hemolysis and the t ransfusion requirement differed markedly. Severe congenital neutropenia (Ko stmann's syndrome)-a disorder never reported before in conjunction with G6P D deficiency-was observed in one case. Levels of white blood cell G6PD acti vity of the three patients were 0-5% of normal controls. Neutrophil oxidati ve and bactericidal activities were inherently impaired in the patient with Kostmann's syndrome, but were well preserved in his two siblings. (C) 2000 Academic Press.