Point Mutations in the Dystrophin Gene

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1992 Mar 15

PMID 1549596

Citations 45

Authors

R G Roberts

M Bobrow

D R Bentley

Affiliations

Soon will be listed here.

Abstract

Defining the range of mutations in genes that cause human disease is essential to determine the mechanisms of genetic variation and the function of gene domains and to perform precise carrier and prenatal diagnosis. The mutations in one-third of Duchenne muscular dystrophy patients remain unknown as they do not involve gross rearrangements of the dystrophin gene. The size and complexity of the gene have prohibited the systematic definition of point mutations. We have developed a method for the identification of these mutations by nested amplification, chemical mismatch detection, and sequencing of reverse transcripts of trace amounts of dystrophin mRNA from peripheral blood lymphocytes. Analysis of the entire coding region (11 kilobases) in seven patients has resulted in detection of a sequence change in each case that is clearly sufficient to cause the disease. All mutations should cause premature translational termination, and the resulting phenotypes are thus equivalent to those caused by frameshifting deletions. The results support a particular functional importance for the C-terminal region of dystrophin. Application of this approach to mutation detection will extend direct carrier and prenatal diagnosis to virtually every affected family.

Citing Articles

A structural genomics approach to investigate Dystrophin mutations and their impact on the molecular pathways of Duchenne muscular dystrophy.

Elasbali A, Anjum F, AlKhamees O, Abu Al-Soud W, Adnan M, Shamsi A Front Genet. 2025; 16:1517707.

PMID: 39981262 PMC: 11841421. DOI: 10.3389/fgene.2025.1517707.

Advances in Dystrophinopathy Diagnosis and Therapy.

Saad F, Siciliano G, Angelini C Biomolecules. 2023; 13(9).

PMID: 37759719 PMC: 10526396. DOI: 10.3390/biom13091319.

Next-Generation Sequencing in a Cohort of Asian Indian Patients with the Duchenne Muscular Dystrophy Phenotype: Diagnostic Yield and Mutation Spectrum.

Nerakh G, Ranganath P, Murugan S J Pediatr Genet. 2021; 10(1):23-28.

PMID: 33552634 PMC: 7853918. DOI: 10.1055/s-0040-1713850.

The position of nonsense mutations can predict the phenotype severity: A survey on the DMD gene.

Torella A, Zanobio M, Zeuli R, Del Vecchio Blanco F, Savarese M, Giugliano T PLoS One. 2020; 15(8):e0237803.

PMID: 32813700 PMC: 7437896. DOI: 10.1371/journal.pone.0237803.

Genetic Variations of Ultraconserved Elements in the Human Genome.

Habic A, Mattick J, Calin G, Krese R, Konc J, Kunej T OMICS. 2019; 23(11):549-559.

PMID: 31689173 PMC: 6857462. DOI: 10.1089/omi.2019.0156.

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