Clinical and molecular characteristics of Thai families with autosomal recessive chronic granulomatous disease

Background: Autosomal recessive chronic granulomatous disease (AR-CGD) is an inherited defect in neutrophil oxidative burst as a result of mutations in one of the three genes, NCF1, NCF2, and CYBA, which respectively encode p47-phox, p67-phox, and p22-phox subunits of the NADPH oxidase complex.Objective: To investigate clinical and molecular characteristics of two unrelated Thai patients with AR-CGD.Methods: A Thai girl who suffered from pulmonary aspergillosis at the age of two months and another unrelated Thai boy presented with recurrent cutaneous abscesses caused by Chromobacterium violaceum since 30 months old, were investigated. The DHR assays revealed abnormalities in both patients but normal results in their mothers, consistent with the diagnosis of AR-CGD. PCR-sequencing of the entire coding regions of NCF1, NCF2, and CYBA was performed.Results: A homozygous c.75_76delGT mutation at the beginning of exon 2 of NCF1 was identified in both individuals. This mutation resulted in a frameshift with premature termination of p47-phox at codon 51 (p.Val25fsX51).Conclusion: The homozygous GT deletion in NCF1 may be a common mutation in Thai patients with AR-CGD. Unlike all other autosomal recessive disorders, AR-CGD caused by NCF1 mutations has a unique mutational pattern, in which there is only one mutation responsible for most patients regardless of their ethnic backgrounds.

Reversible prostaglandin-induced cortical hyperostosis in an infant without 3040C→T mutation in COL1A1

Background: A hereditary form of infantile cortical hyperostosis (ICH), known as Caffey disease, was recently found to be caused by a heterozygous 3040C → T mutation in the COL1A1 gene. Objective: To determine whether a similar mutation was also responsible for a sporadic case of ICH. Methods: We identified a Thai male infant who was a sporadic case of ICH. He had symmetric cortical hyperostosis of all of his long bones, clavicles, and ribs occurring after a prolonged infusion of prostaglandin E1 (PGE1) for a cyanotic congenital heart disease. Mutation analysis of COL1A1 was performed in the patient and his parents by restriction enzyme digestion of PCR products. Results: The particular mutation was not found in our case and in his parents. A follow-up after 15 months demonstrated that the child had normal growth and development. Repeated imaging studies revealed markedly decreased cortical thickenings of the affected bones. Conclusion: Our findings confirm that PGE1-induced cortical hyperostosis is reversible and does not associate with the COL1A1 3040C→T mutation. Keywords: COL1A1, infantile cortical hyperostosis, prostaglandin, reversible.