Identification of a Homozygous PEX26 Mutation in a Heimler Syndrome Patient
| Autor: | Yuichi Abe, Jung-Wook Kim, Young-Jae Kim, Youn Jung Kim, Yukio Fujiki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Proband temperature sensitivity Male Amelogenesis Imperfecta Hearing Loss Sensorineural Mutant Nails Malformed CHO Cells 030105 genetics & heredity Biology QH426-470 whole exome sequencing 03 medical and health sciences Cricetulus Cricetinae medicine Genetics Animals Humans Amelogenesis imperfecta Child Gene Genetics (clinical) Exome sequencing hearing loss Heimler syndrome Communication Homozygote Chromosome PEX26 Membrane Proteins medicine.disease Protein Transport 030104 developmental biology Phenotype Mutation (genetic algorithm) Mutation Sensorineural hearing loss |
| Zdroj: | Genes Genes, Vol 12, Iss 646, p 646 (2021) |
| ISSN: | 2073-4425 |
| Popis: | 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 PEX26 gene. We verified “temperature sensitivity (ts)” of patient-derived Pex26-L169P by expression in pex26 CHO mutant ZP167 cells to determine the effect of the L169P mutation on Pex26 function. The L169P mutation causes a mild ts-cellular phenotype representing the decreased peroxisomal import of catalase. This study supports the finding that the recessive mutations in PEX26 are associated with Heimler syndrome and demonstrates the importance of an early and correct diagnosis. |
| Databáze: | OpenAIRE |
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