A novel mutation in GPR68 causes hypomaturation amelogenesis imperfecta.

Area of Science:

• Genetics and Molecular Biology
• Dental and Oral Health
• Biochemistry

Background:

• Amelogenesis imperfecta (AI) is a group of inherited enamel disorders.
• Hypomaturation AI presents with fragile, discolored enamel.
• The genetic basis of many AI subtypes remains unclear.

Purpose of the Study:

• To identify the genetic cause of hypomaturation AI in a Chinese family.
• To characterize the enamel structure affected by GPR68 mutations.
• To elucidate the role of GPR68 in amelogenesis.

Main Methods:

• Recruited a Chinese family with generalized hypomaturation AI.
• Utilized scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) for enamel analysis.
• Performed whole exome sequencing (WES) and Sanger sequencing to identify and confirm mutations.
• Conducted bioinformatics analysis to assess mutation impact.

Main Results:

• The proband exhibited hypomaturation AI with fragile, discolored enamel.
• AI enamel showed structural abnormalities, reduced calcium and phosphorus, and increased oxygen content.
• A novel homozygous mutation in G protein-coupled receptor 68 (GPR68) (c.149T>A, p.Ile50Asn) was identified.
• Bioinformatics suggested the mutation affects protein stability and conformation.

Conclusions:

• A novel homozygous GPR68 mutation is causative for hypomaturation AI.
• This study provides the first description of GPR68 mutation effects on enamel structure.
• Findings offer new genetic evidence linking GPR68 to hypomaturation AI.