Asymptomatic isolated human glycerol kinase deficiency associated with splice-site mutations and nonsense-mediated decay of mutant RNA

Yao Hua Zhang, Bing Ling Huang, Ishwarlal Jialal, Hope Northrup, Edward R B Mccabe, Katrina M. Dipple

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Isolated glycerol kinase deficiency (GKD) is an X-linked inborn error of metabolism that is either symptomatic or asymptomatic. GKD is due to deletions of, or mutations within, the GK gene, and there is no genotype-phenotype correlation. We identified three patients with asymptomatic GKD, determined that they had GK splice-site mutations, and studied the stability of their GK mRNA to understand the molecular mechanism of the GKD. All three patient mutations caused a frameshift and introduction of a premature stop codon. A fourth patient had an Alu insertion in intron 4 that led to alternative splicing. To study the effect of splice-site mutations on RNA species, we performed reverse transcriptase PCR and found only normal-sized products for all patients. Incubation with anisomycin to block nonsense-mediated decay (NMD), revealed two RNA species for each individual. Sequence analysis revealed that the larger bands represented the wild-type GK RNA and smaller bands represented mutant misspliced RNA, suggesting that the abnormal RNA species were targeted by NMD. Normal RNA species observed in each patient are likely responsible for their mild phenotypes. We speculate that influences on RNA processing and protein stability represent modifiers of the GKD phenotype.

Original languageEnglish (US)
Pages (from-to)590-592
Number of pages3
JournalPediatric Research
Volume59
Issue number4 PART 1
DOIs
StatePublished - Apr 2006

Fingerprint

Nonsense Codon
RNA Stability
RNA
Mutation
Anisomycin
Phenotype
Inborn Errors Metabolism
Protein Stability
Sequence Deletion
Alternative Splicing
Genetic Association Studies
Reverse Transcriptase Polymerase Chain Reaction
Introns
Sequence Analysis
Hyperglycerolemia
Messenger RNA
Genes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Asymptomatic isolated human glycerol kinase deficiency associated with splice-site mutations and nonsense-mediated decay of mutant RNA. / Zhang, Yao Hua; Huang, Bing Ling; Jialal, Ishwarlal; Northrup, Hope; Mccabe, Edward R B; Dipple, Katrina M.

In: Pediatric Research, Vol. 59, No. 4 PART 1, 04.2006, p. 590-592.

Research output: Contribution to journalArticle

Zhang, Yao Hua ; Huang, Bing Ling ; Jialal, Ishwarlal ; Northrup, Hope ; Mccabe, Edward R B ; Dipple, Katrina M. / Asymptomatic isolated human glycerol kinase deficiency associated with splice-site mutations and nonsense-mediated decay of mutant RNA. In: Pediatric Research. 2006 ; Vol. 59, No. 4 PART 1. pp. 590-592.
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