Alleles, deletion Mutations

In a patient with retinoblastoma, the RB gene is either mutated in both alleles or, when only one allele is mutated, the other allelic gene is deleted. This occurs quite often in... 

Vortmeyer AO, Lubensky lA, Fogt F, et ak Allelic deletion and mutation of the von Hippel-Lindau (VHL) tumor suppressor gene in pancreatic microcystic adenomas. Am J Pathol. 1997 151 951-956. 

Gortz B, Roth J, Krahenmann A, et al. Mutations and allelic deletions of the MENl gene are associated with a subset of sporadic endocrine pancreatic and neuroendocrine tumors and not restricted to foregut neoplasms. Am J Pathol. 1999 154 429-... 

Refractory mutations are difficult to detect due to the nature of the molecular defects. If the genomic region is deleted from the mutant allele, the PCR product from genomic DNA will lead to a false conclusion that this gene region is wild-type. Other mutations affect the expression or processing of mRNA from the affected allele, through mutations of promoter... 

Figure 1. Molecular structure of the mouse short-chain acyl-CoA dehydrogenase gene including the deletion mutation found in BALB/cByJ mice. Adapted and redrawn from previous publications."- A. The fine genomic structure of the deletion mutation, b. Molecular structure of the approximately normal size Acads mRNA from the mutant allele. This consists of an RNA copy of the deleted gene sequence with no splicing, c. Molecular structure of the short Acads mRNA from the mutant allele. This consists of a missplked mRNA from exon 8 to a cryptic splice site in exon 10.

GSH-S deficiency is a more frequent cause of GSH deficiency (HI7), and more than 20 families with this enzyme deficiency have been reported since the first report by Oort et al. (05). There are two distinct types of GSH-S deficiency with different clinical pictures. In the red blood cell type, the enzyme defect is limited to red blood cells and the only clinical presentation is mild hemolysis. In the generalized type, the deficiency is also found in tissues other than red blood cells, and the patients show not only chronic hemolytic anemia but also metabolic acidosis with marked 5-oxoprolinuria and neurologic manifestations including mental retardation. The precise mechanism of these two different phenotypes remains to be elucidated, because the existence of tissue-specific isozymes is not clear. Seven mutations at the GSH-S locus on six alleles—four missense mutations, two deletions, and one splice site mutation—have been identified (S14). 

Approximately 90% of CF patients carry a loss-of-function CFTR mutation on at least one allele that results in deletion of phenylalanine 508 (F508del) in the first CFTR nucleotide-binding domain [7]. The F508del prevents the proper domain folding and assembly of the multidomain CFTR protein during its biogenesis in the endoplasmic... 

A 1-year-old toddler with cystic fibrosis (CF) is seen by his physician for an upper respiratory infection with Pseudomonas aeruginosa. He is started on oral norfloxacin and referred to a CF center as i potential candidate for gene therapy. Prior genetic testing of the patient identified the mutation causing cystic fibrosis as a 3-base-pair deletion in esan 10 of the CF gene. The nucleotide sequences f codons 506-511 in this region of the normal and mutant alleles are compared below. 

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