Point mutation in a family with hyperproinsulinemia detected by single stranded conformational polymorphism

Area of Science:

• Human Genetics
• Molecular Biology
• Endocrinology

Background:

• Familial hyperproinsulinemia is a rare genetic disorder characterized by elevated proinsulin levels.
• Previous reports have documented familial hyperproinsulinemia, with this study detailing the fifth reported case.
• Understanding the genetic basis of this disorder is crucial for diagnosis and potential therapeutic strategies.

Observation:

• A 63-year-old Japanese male, the propositus, presented with familial hyperproinsulinemia.
• Serum proinsulin analysis indicated an intermediate cleavage defect at the B-C junction.
• Genetic sequencing focused on exon 3 of the insulin gene, encompassing the C-A junction.

Findings:

• A specific point mutation was identified in one allele of the insulin gene, altering codon 65 from arginine to histidine (CGT to CAT).
• This mutation is identical to one previously found in unrelated families across different races, suggesting CpG dinucleotides as mutation hotspots.
• Polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) successfully detected this mutation in family members, including the propositus's daughter and one grandson, who were heterozygous.

Implications:

• The findings confirm the genetic defect responsible for familial hyperproinsulinemia in this family.
• PCR-SSCP is validated as a sensitive method for detecting this specific mutation within families.
• The recurrence of this mutation reinforces the concept of CpG sites as mutation hotspots in the human genome.