Identification of a Homozygous PEX26 Mutation in a Heimler Syndrome Patient

• Published in: Genes 2021-04, Vol.12 (5), p.646
• Main Authors: Kim, Youn Jung, Abe, Yuichi, Kim, Young-Jae, Fujiki, Yukio, Kim, Jung-Wook
• Format: Article
• Language: English
• Subjects: Amelogenesis imperfecta; Catalase; Chromosomes; Cochlea; Communication; Dentition; DNA sequencing; Enamel; Etiology; Genomes; Genotype & phenotype; Hearing loss; Mutation; Peripheral blood; Phenotypes; Sequence analysis; Teeth
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12050646

This study aimed to identify the molecular genetic etiology of an 8-year-old boy with amelogenesis imperfecta in permanent dentition. Bilateral cochlear implants were placed due to sensorineural hearing loss, and there was no other family member with a similar phenotype. Peripheral blood samples were collected with the understanding and written consent of the participating family members. A constitutional chromosome study was performed for the proband. Genomic DNA was isolated, and whole exome sequencing was performed. A series of bioinformatic analyses were performed with the obtained paired-end sequencing reads, and the variants were filtered and annotated with dbSNP147. There was no abnormality in the constitutional chromosome study. Whole exome sequencing analysis with trio samples identified a homozygous mutation (c.506T>C, p. (Leu169Pro)) in the gene. We verified temperature sensitivity ( )" of patient-derived Pex26-L169P by expression in CHO mutant ZP167 cells to determine the effect of the L169P mutation on Pex26 function. The L169P mutation causes a mild -cellular phenotype representing the decreased peroxisomal import of catalase. This study supports the finding that the recessive mutations in are associated with Heimler syndrome and demonstrates the importance of an early and correct diagnosis.