IADR Abstract Archives
A Novel PCCB Mutation Associated with Propionic Acidemia and Abnormal Tooth Development
Objectives: Propionic acidemia (PA) is an autosomal recessive metabolic disorder caused by defects in the propionyl-CoA carboxylase (PCC) enzyme. It has been shown that mutations in either the PCCA (chromosome 13q32) or PCCB (chromosome 3q21-q22) genes encoding alpha or beta subunits of the PCC enzyme, respectively, can cause propionic acidemia. PCCA mutations have been identified in a small number of Thai patients whereas PCCB mutations have never been reported in Thailand. This study aimed to investigate dental characteristics and PA-causing genomic variants in a Thai family. A novel finding will expand genetic knowledge of the disease
Methods: Propionic acidemia was diagnosed by newborn screening using tandem mass spectrometry (MS/MS) and urine organic acid analysis using gas chromatography and mass spectrometry. Whole Exome Sequencing (WES) was used to identify the disease-causing mutation of PA. The presence of the identified variant was confirmed by Sanger sequencing.
Results: The proband was born to consanguineous parents. He had congenitally missing teeth and fusion of primary mandibular incisors. WES revealed a novel homozygous frameshift insertion (NM_000532:c.379_380insA:p.T127NfsX160) in the exon4 of the PCCB gene. His parents were heterozygous for the mutation. The identified mutation has never been reported in public database, including NCBI37 reference human genome (the version used for 1000Genomes project), NHLBI Exome Variant Server (EVS), and in-house database (100 exome Thai controls). No previous studies have shown dental phenotypes of PA.
Conclusions: We revealed for the first time that hypodontia and tooth fusion could occur as part of PA. A novel homozygous frameshift insertion, c.379_380insA:p.T127NfsX160, in the PCCB gene was discovered. The mutation was expected to result in unstable mRNA, which might be degraded by nonsense mediated mRNA decay. Whether the abnormal tooth formation relates to PCCB mutations requires further studies.
Methods: Propionic acidemia was diagnosed by newborn screening using tandem mass spectrometry (MS/MS) and urine organic acid analysis using gas chromatography and mass spectrometry. Whole Exome Sequencing (WES) was used to identify the disease-causing mutation of PA. The presence of the identified variant was confirmed by Sanger sequencing.
Results: The proband was born to consanguineous parents. He had congenitally missing teeth and fusion of primary mandibular incisors. WES revealed a novel homozygous frameshift insertion (NM_000532:c.379_380insA:p.T127NfsX160) in the exon4 of the PCCB gene. His parents were heterozygous for the mutation. The identified mutation has never been reported in public database, including NCBI37 reference human genome (the version used for 1000Genomes project), NHLBI Exome Variant Server (EVS), and in-house database (100 exome Thai controls). No previous studies have shown dental phenotypes of PA.
Conclusions: We revealed for the first time that hypodontia and tooth fusion could occur as part of PA. A novel homozygous frameshift insertion, c.379_380insA:p.T127NfsX160, in the PCCB gene was discovered. The mutation was expected to result in unstable mRNA, which might be degraded by nonsense mediated mRNA decay. Whether the abnormal tooth formation relates to PCCB mutations requires further studies.