Heimler Syndrome With Tooth Agenesis, Abnormal Enamel and Dentin Mineralization, Root Maldevelopment, and PEX1...

Area of Science:

• Genetics
• Oral Biology
• Medical Genetics

Background:

• Heimler syndrome is a rare genetic disorder.
• It is characterized by amelogenesis imperfecta, sensorineural hearing loss, retinitis pigmentosa, and nail defects.
• Biallelic variants in PEX1 and PEX6 genes are implicated.

Purpose of the Study:

• To identify the genetic variant in a patient with Heimler syndrome.
• To analyze the dental characteristics of the affected patient.
• To investigate the molecular mechanisms underlying the syndrome.

Main Methods:

• Clinical and radiographic examination.
• Whole exome sequencing.
• Scanning electron microscopy, micro-computed tomography, and immunohistochemical study of Pex1.
• Mutant protein modeling.

Main Results:

• An 18-year-old male with Heimler syndrome was found to have compound heterozygous mutations in the PEX1 gene (c.2966T>C; p.Ile989Thr and c.2097_2098insT; p.Ile700TyrfsTer42).
• Clinical findings included amelogenesis imperfecta, sensorineural hearing loss, retinitis pigmentosa, leukonychia, arachnodactyly, tooth agenesis, microdontia, root maldevelopment, and failure of tooth eruption.
• SEM revealed enamel and dentin dysmineralization; protein modeling suggested non-viable or disrupted protein interactions.

Conclusions:

• This study identifies novel PEX1 mutations associated with Heimler syndrome.
• It expands the spectrum of clinical manifestations to include arachnodactyly and various dental anomalies.
• The findings provide insights into the pathomechanisms of Heimler syndrome, particularly concerning dental and skeletal development.