A novel mutation detected by temporal temperature gradient gel electrophoresis led to the confirmative prenatal diagnosis of a Hispanic CF family

Abstract

Mutational analysis of 30 recurrent known mutations detects only about 58% of Hispanic cystic fibrosis (CF) chromosomes. The low mutation detection rate has greatly hindered prenatal diagnosis and carrier testing of Hispanic families who have multiple affected children with unidentified cystic fibrosis transmembrane conductance regulator (CFTR) mutations. We recently employed a temporal temperature gradient gel electrophoresis (TTGE) method to effectively scan unknown mutations in the entire CFTR gene. A novel mutation, 2105‐2117 del13insAGAAA was identified in a Hispanic family heterozygous for ΔF508. The discovery of the devastating mutation facilitated the prenatal diagnosis for this family who already had two severely affected children. The fetus was found to be a compound heterozygote of ΔF508/2105‐2117 del13insAGAAA. This case emphasizes the importance of whole gene mutational analysis in patients with a clinical diagnosis of CF, but without the identifiable DNA mutations by routine mutation analysis. Finding of CF mutations in the patient would allow proper genetic counselling and prenatal and carrier detection of at‐risk family members. Copyright © 2000 John Wiley & Sons, Ltd.

Cystic fibrosis in a Hispanic adolescent

“…Coupled with worse clinical outcomes and lower socioeconomic status, these factors contribute to an annual risk of mortality that is 85% higher than non‐Hispanics . Through the limited number of studies examining the mutation spectrum in the Hispanic population in the US, there appears to be a pattern of increased frequency of specific mutations (i.e., 3876delA) and stop mutations, suggesting that an ethnicity‐specific mutation panel defined by techniques that identify alterations in CFTR coding regions and transcription would facilitate diagnosis in pancreatic insufficient and sufficient patients.…”

1154insTC is not a rare CFTR mutation

“…Using mutation screening methods, such as denaturating gradient gel electrophoresis (DGGE) and temporal temperature gradient gel electrophoresis (TTGE), followed by sequencing has greatly improved the detection rate [Macek et al, 1997; Wong et al, 2001a]. Identification of CFTR mutations is important in genetic counseling and prenatal diagnosis particularly in families with multiple affected children [Wong et al, 2000; Wong et al, 2001b]. During the course of identifying unknown mutations in 60 Hispanic and 20 Caucasian patients, we found two 1154insTC mutant alleles, both in Caucasians.…”

Enhanced recognition of cystic fibrosis W1282X DNA point mutation by chiral peptide nucleic acid probes by a surface plasmon resonance biosensor

“…We focused our attention on the W1282X point mutation (Shoshani et al, 1992) of the CF gene (Vidaud et al, 1990;Wong et al, 2000), which is the most common CF mutation in the Ashkenazi Jewish population, where it is present on 50-60% of CF chromosomes. Patients homozygous for the W1282X mutation and patients heterozygous for the delta-F508 and W1282X mutations had similarly severe diseases, shown by pancreatic insufficiency, high incidence of meconium ileus, poor nutritional status, and variable pulmonary function and complications.…”