An unusual insertion/deletion in the gene encoding the beta-subunit of propionyl-CoA carboxylase is a frequent mutation in Caucasian propionic acidemia.

Abstract

Propionic acidemia is an inherited disorder of organic acid metabolism that is caused by deficiency of propionyl-CoA carboxylase (PCC; EC 6.4

Extreme androgen resistance in a kindred with a novel insertion/deletion mutation in exon 5 of the androgen receptor gene

“…Similar structural disorders have been published for other genes causing human genetic diseases, where deletions and/or duplications of short sequences similarly lead to the synthesis of truncated proteins Krawczak and Cooper 1991). Examples of genes that have been found to contain these types of mutations are PCCB (Tahara et al 1990), IDUA (Moskowitz et al 1993), WT1 (Huff et al 1995), FAA (Levran et al 1997), HBA2 (Oron-Karni et al 1997, and BRCA1 (Hardouin et al 2000). More recently, a similar rearrangement to ours was found in CYP27B1 from a patient with 1a-hydroxylase deficiency (Wang et al 2002).…”

“…Based on these and other observations (Levinson and Gutman 1987;Tahara et al 1990;Oner et al 1991;Tatsumi et al 1995), we viewed a slippage-misalignment as the probable mechanism in generating this mutation. As mentioned above, it has long been recognized that small deletions and also small insertions can arise from slippage and mispairing of two homologous DNA sequences during DNA replication.…”

The molecular defect in propionic acidemia: Exon skipping caused by an 8-bp deletion from an intron in the PCCB allele

“…We also suggest that the frameshift and consequent premature termination were responsible for the lack of activity and protein instability that resulted in PCC deficiency in this patient. Surprisingly, two mutations that have been described in Caucasian propionic acidemia (Tahara et al 1990;Lamhonwah et al 1990) are also located in this exon, although the contribution of the peptide specified by this exon to I]PCC enzymatic activity is not known. The gene structure adjacent to this exon may be a hot spot for mutation.…”

“…1, dotted line and Fig.2) in one of the patient's c D N A sequences. This 101 bp sequence corresponded precisely to one exon of the PCC gene, which was identified by Tahara et al (1990). This result could be explained by a partial gene deletion or by an R N A splicing mutation that efficiently removed the coding sequences of one exon.…”

“…Partial human cDNA clones encoding the ~ and the [3 subunits have been isolated (Lamhonwah et al 1986). Recent studies have identified two different mutations in the [3 subunit of PCC (13PCC) in Caucasian propionic acidemia (Tahara et al 1990;Lamhonwah et al 1990). An unusual insertion/ deletion and an in-frame 3-bp deletion were identified in the same exon.…”