Incomplete nonsense-mediated decay facilitates detection of a multi-exonic deletion mutation in SGCE

Jianfeng Xiao, Ma Nance, Mark Ledoux

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Mutations in SGCE represent the major cause of the myoclonus-dystonia syndrome (DYT11), an autosomal dominant disorder of reduced penetrance. Virtually all affected individuals have myoclonus, which is concentrated in the upper extremities, neck and trunk. Over half of patients have dystonia, usually affecting the neck or arms. SGCE is maternally imprinted. Of the more than 70 SGCE mutations reported in the literature, 18 are large deletions disrupting at least one exon. Therefore, testing for exonic deletions should be considered in individuals with a classic phenotype in whom Sanger sequencing is unrevealing. However, standard methodologies for detection of exonic deletion mutations are expensive, labor intensive and can produce false negatives. Herein, we report the use of cDNA derived from leukocyte RNA to identify a deletion mutation (exons 4 and 5) of SGCE in a family with DYT11. Residual RNA from incomplete nonsense-mediated decay permitted reverse transcription to cDNA. Breakpoints of the 8939bp heterozygous deletion were then defined with long-range polymerase chain reaction and Sanger sequencing. Use of cDNA generated by reverse transcription of leukocyte RNA can reduce the costs associated with diagnostic genetic testing and can facilitate detection of deletion mutations.

Original languageEnglish (US)
Pages (from-to)276-280
Number of pages5
JournalClinical Genetics
Volume84
Issue number3
DOIs
StatePublished - Sep 1 2013

Fingerprint

Sequence Deletion
Complementary DNA
RNA
Reverse Transcription
Exons
Leukocytes
Neck
Mutation
Myoclonus
Penetrance
Dystonia
Genetic Testing
Upper Extremity
Arm
Phenotype
Costs and Cost Analysis
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Incomplete nonsense-mediated decay facilitates detection of a multi-exonic deletion mutation in SGCE. / Xiao, Jianfeng; Nance, Ma; Ledoux, Mark.

In: Clinical Genetics, Vol. 84, No. 3, 01.09.2013, p. 276-280.

Research output: Contribution to journalArticle

@article{b6f59f5596304b9fbc51c0537b96422d,
title = "Incomplete nonsense-mediated decay facilitates detection of a multi-exonic deletion mutation in SGCE",
abstract = "Mutations in SGCE represent the major cause of the myoclonus-dystonia syndrome (DYT11), an autosomal dominant disorder of reduced penetrance. Virtually all affected individuals have myoclonus, which is concentrated in the upper extremities, neck and trunk. Over half of patients have dystonia, usually affecting the neck or arms. SGCE is maternally imprinted. Of the more than 70 SGCE mutations reported in the literature, 18 are large deletions disrupting at least one exon. Therefore, testing for exonic deletions should be considered in individuals with a classic phenotype in whom Sanger sequencing is unrevealing. However, standard methodologies for detection of exonic deletion mutations are expensive, labor intensive and can produce false negatives. Herein, we report the use of cDNA derived from leukocyte RNA to identify a deletion mutation (exons 4 and 5) of SGCE in a family with DYT11. Residual RNA from incomplete nonsense-mediated decay permitted reverse transcription to cDNA. Breakpoints of the 8939bp heterozygous deletion were then defined with long-range polymerase chain reaction and Sanger sequencing. Use of cDNA generated by reverse transcription of leukocyte RNA can reduce the costs associated with diagnostic genetic testing and can facilitate detection of deletion mutations.",
author = "Jianfeng Xiao and Ma Nance and Mark Ledoux",
year = "2013",
month = "9",
day = "1",
doi = "10.1111/cge.12059",
language = "English (US)",
volume = "84",
pages = "276--280",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Incomplete nonsense-mediated decay facilitates detection of a multi-exonic deletion mutation in SGCE

AU - Xiao, Jianfeng

AU - Nance, Ma

AU - Ledoux, Mark

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Mutations in SGCE represent the major cause of the myoclonus-dystonia syndrome (DYT11), an autosomal dominant disorder of reduced penetrance. Virtually all affected individuals have myoclonus, which is concentrated in the upper extremities, neck and trunk. Over half of patients have dystonia, usually affecting the neck or arms. SGCE is maternally imprinted. Of the more than 70 SGCE mutations reported in the literature, 18 are large deletions disrupting at least one exon. Therefore, testing for exonic deletions should be considered in individuals with a classic phenotype in whom Sanger sequencing is unrevealing. However, standard methodologies for detection of exonic deletion mutations are expensive, labor intensive and can produce false negatives. Herein, we report the use of cDNA derived from leukocyte RNA to identify a deletion mutation (exons 4 and 5) of SGCE in a family with DYT11. Residual RNA from incomplete nonsense-mediated decay permitted reverse transcription to cDNA. Breakpoints of the 8939bp heterozygous deletion were then defined with long-range polymerase chain reaction and Sanger sequencing. Use of cDNA generated by reverse transcription of leukocyte RNA can reduce the costs associated with diagnostic genetic testing and can facilitate detection of deletion mutations.

AB - Mutations in SGCE represent the major cause of the myoclonus-dystonia syndrome (DYT11), an autosomal dominant disorder of reduced penetrance. Virtually all affected individuals have myoclonus, which is concentrated in the upper extremities, neck and trunk. Over half of patients have dystonia, usually affecting the neck or arms. SGCE is maternally imprinted. Of the more than 70 SGCE mutations reported in the literature, 18 are large deletions disrupting at least one exon. Therefore, testing for exonic deletions should be considered in individuals with a classic phenotype in whom Sanger sequencing is unrevealing. However, standard methodologies for detection of exonic deletion mutations are expensive, labor intensive and can produce false negatives. Herein, we report the use of cDNA derived from leukocyte RNA to identify a deletion mutation (exons 4 and 5) of SGCE in a family with DYT11. Residual RNA from incomplete nonsense-mediated decay permitted reverse transcription to cDNA. Breakpoints of the 8939bp heterozygous deletion were then defined with long-range polymerase chain reaction and Sanger sequencing. Use of cDNA generated by reverse transcription of leukocyte RNA can reduce the costs associated with diagnostic genetic testing and can facilitate detection of deletion mutations.

UR - http://www.scopus.com/inward/record.url?scp=84881611918&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881611918&partnerID=8YFLogxK

U2 - 10.1111/cge.12059

DO - 10.1111/cge.12059

M3 - Article

C2 - 23140253

AN - SCOPUS:84881611918

VL - 84

SP - 276

EP - 280

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 3

ER -