A Thai family with hereditary pancreatitis and increased cancer risk due to a mutation in PRSS1 gene

AIM: To investigate mutation of serine protease 1-cationic trypsinogen (CT, PRSS1) gene in members of a Thai family with hereditary pancreatitis and pancreatic cancer.METHODS: Polymerase chain reaction and direct sequencing were performed to analyze the PRSS1 gene in two members of the family affected by pancreatitis.Allele specific amplification (ASA) method was then developed to detect the mutation of the PRSS1 gene in all available members of the family and normal control subjects.RESULTS: A cytosine (C) to thymine (T) mutation at position 2441 (g.2441C＞T) of the PRSS1 gene, which results in a substitution of arginine by cysteine at position 116 (R116C) of CT, was identified by direct sequencing in both clinically affected members of the family but was not found in the unaffected member. This mutation, which might be arising from deamination of methylated cytosine in CpG dinucleotide of codon 116 (CGT＞FGT), was also detected by the ASA method in the two affected members and a proband's brother but was not observed in unaffected members and 54 normal control subjects.CONCLUSION: Autosomal dominant pancreatitis with increased cancer risk in the studied Thai family is most likely due to missense (R116C) mutation in the PRSS1gene.

HNF1A mutation in a Thai patient with maturity-onset diabetes of the young: A case report

BACKGROUND Maturity-onset diabetes of the young(MODY)is the most common form of monogenic diabetes.The disease is transmitted in autosomal dominant mode and diabetes is usually diagnosed before age 25 year.MODY 3 is caused by mutation of hepatocyte nuclear factor(HNF)1A genes and is the most common MODY subtype.Diagnosis of MODY 3 is crucial since glycemic control can be accomplished by very low dose of sulfonylurea.In this report we described a Thai MODY 3 patient who had excellence plasma glucose control by treating with glicazide 20 mg per day and insulin therapy can be discontinued.CASE SUMMARY A 31-year-old woman was diagnosed diabetes mellitus at 14 years old.The disease was transmitted from her grandmother and mother compatible with autosomal dominant inheritance.Sanger sequencing of proband’s DNA identified mutation of HNF1A at codon 203 which changed amino acid from arginine to cysteine(R203C).This mutation was carried only by family members who have diabetes.The patient has been treated effectively with a combination of oral hypoglycemic agents and must include a very low dose of glicazide(20 mg/d).Insulin therapy was successfully discontinued.CONCLUSION We demonstrated a first case of pharmacogenetics in Thai MODY 3 patient.Our findings underscore the essential role of molecular genetics in diagnosis and guidance of appropriate treatment of diabetes mellitus in particular patient.