ABSTRACT
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.
ABSTRACT
Background: Crigler-Najjar syndrome (CN) clinically manifests as intense unconjugated hyperbilirubinemia without evidence of hemolysis. At present, over 90 genetic variations such as mutations, insertions, or deletions have been described in the five exons of the UDP-glucuronosyltransferase (UGT1A1) gene responsible for defect of bilirubin conjugation.Objective: To report a case of a female CN type I child who presented with unconjugated hyperbilirubinemia, normal liver function tests, and normal ultrasonographic images of the liver.Results: Peak total bilirubin in this patient was 27.6 mg/dL. She developed kernicterus despite prolonged daily home phototherapy. Exons 1-5 of the UGT1A1 gene were amplified by polymerase chain reaction (PCR) and the UGT1A1 gene was screened for mutations by direct DNA sequencing. Molecular genetic analysis showed that this patient was homozygous for a nonsense mutation at nucleotide number 715 (715C→T) in exon 1 resulting in the replacement of glutamine (CAG, amino acid 239) by a stop codon (TAG).Conclusion: Detection of this genetic defect is essential for gene therapy and can be used as a prenatal screening test to identify the affected offspring.
ABSTRACT
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.