A Novel Cryptic Exon Identified in the 3' Region of Intron 2 of the Human Dystrophin Gene

Overview

Journal J Hum Genet

Specialty Genetics

Date 2005 Sep 1

PMID 16133659

Citations 15

Authors

Van Khanh Tran

Zhujun Zhang

Mariko Yagi

Atsushi Nishiyama

Yasuaki Habara

Yasuhiro Takeshima

Masafumi Matsuo

Affiliations

Soon will be listed here.

Abstract

The dystrophin gene, which is mutated in Duchenne muscular dystrophy (DMD), is the largest known human gene and is characterized by the huge size of its introns. Intron 2, the second largest intron, is 170-kb long and has been shown to include a 140-bp cryptic exon (exon 2a) in its 5' region. The rest of this intron has no known function. In this study, we find that another cryptic exon, located in the 3' region of intron 2, is activated in a promoter- or tissue-specific manner. An unknown 98-bp insertion precisely between exons 2 and 3 was identified in one of the dystrophin mRNAs from lymphocytes of a DMD patient with a duplication of exon 2. This 98-bp sequence, located in the 3' region of intron 2, was found to possess a branch point, acceptor and donor splice-site consensus sequences, and an exonic splicing enhancer sequence, and thus is a novel exon, which we named "exon 2b." In lymphocytes, exon 2b incorporation was detected in the muscle-specific, promoter-driven transcript. Five of 20 normal human tissue mRNAs, including cardiac and skeletal muscle mRNAs, were confirmed to contain a fragment extending from exon 1 to exon 2b by reverse transcription PCR amplification, indicating that exon 2b is activated in a tissue-specific manner. This provides a clue to a novel cause of dystrophinopathy.

Citing Articles

Analysis of Pathogenic Pseudoexons Reveals Novel Mechanisms Driving Cryptic Splicing.

Keegan N, Wilton S, Fletcher S Front Genet. 2022; 12:806946.

PMID: 35140743 PMC: 8819188. DOI: 10.3389/fgene.2021.806946.

Intronic Alternative Polyadenylation in the Middle of the Gene Produces Half-Size N-Terminal Dystrophin with a Potential Implication of ECG Abnormalities of DMD Patients.

Rani A, Yamamoto T, Kawaguchi T, Maeta K, Awano H, Nishio H Int J Mol Sci. 2020; 21(10).

PMID: 32443516 PMC: 7278912. DOI: 10.3390/ijms21103555.

Pseudoexons of the DMD Gene.

Keegan N J Neuromuscul Dis. 2020; 7(2):77-95.

PMID: 32176650 PMC: 7175933. DOI: 10.3233/JND-190431.

The CYCLIN-DEPENDENT KINASE Module of the Mediator Complex Promotes Flowering and Reproductive Development in Pea.

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Cardiac Dysfunction in Duchenne Muscular Dystrophy Is Less Frequent in Patients With Mutations in the Dystrophin Dp116 Coding Region Than in Other Regions.

Yamamoto T, Awano H, Zhang Z, Sakuma M, Kitaaki S, Matsumoto M Circ Genom Precis Med. 2018; 11(1):e001782.

PMID: 29874176 PMC: 6319568. DOI: 10.1161/CIRCGEN.117.001782.

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