BACKGROUND: Recent methodological advances have improved the detection rate for dystrophin mutations, but there are no published studies that have measured the clinical utility of these protocols for carrier detection compared with conventional carrier testing protocols that use pedigree, serum creatine kinase levels and linkage analysis. METHODS AND SUBJECTS: The clinical utility of a combined mutation detection protocol was measured. It involved quantitative PCR procedures followed by DNA sequence analysis for the identification of dystrophin mutation carriers in 2101 women at risk of being carriers from 348 mutation-known Duchenne or Becker muscular dystrophy pedigrees. RESULTS: The combined mutation detection protocol identified a mutation in 96% and 82% of index cases of Duchenne muscular dystrophy and Becker muscular dystrophy, respectively. An additional 692 (33%) potential carriers were correctly classified by the combined mutation detection protocol compared with pedigree, serum creatine kinase levels and linkage analysis. Significantly lower mutation carrier rates were identified in the mothers of isolated cases with deletion mutations than predicted from theoretical considerations, but these findings were not confirmed for duplication and DNA sequence mutations. CONCLUSIONS: There are significant clinical benefits to be gained from a combined mutation detection protocol for carrier detection. It is recommended that mutation-specific carrier frequencies for the different classes of dystrophin mutations should be taken into account in genetic counselling practice.
BACKGROUND: Recent methodological advances have improved the detection rate for dystrophin mutations, but there are no published studies that have measured the clinical utility of these protocols for carrier detection compared with conventional carrier testing protocols that use pedigree, serum creatine kinase levels and linkage analysis. METHODS AND SUBJECTS: The clinical utility of a combined mutation detection protocol was measured. It involved quantitative PCR procedures followed by DNA sequence analysis for the identification of dystrophin mutation carriers in 2101 women at risk of being carriers from 348 mutation-known Duchenne or Becker muscular dystrophy pedigrees. RESULTS: The combined mutation detection protocol identified a mutation in 96% and 82% of index cases of Duchenne muscular dystrophy and Becker muscular dystrophy, respectively. An additional 692 (33%) potential carriers were correctly classified by the combined mutation detection protocol compared with pedigree, serum creatine kinase levels and linkage analysis. Significantly lower mutation carrier rates were identified in the mothers of isolated cases with deletion mutations than predicted from theoretical considerations, but these findings were not confirmed for duplication and DNA sequence mutations. CONCLUSIONS: There are significant clinical benefits to be gained from a combined mutation detection protocol for carrier detection. It is recommended that mutation-specific carrier frequencies for the different classes of dystrophin mutations should be taken into account in genetic counselling practice.
Authors: K M Dent; D M Dunn; A C von Niederhausern; A T Aoyagi; L Kerr; M B Bromberg; K J Hart; T Tuohy; S White; J T den Dunnen; R B Weiss; K M Flanigan Journal: Am J Med Genet A Date: 2005-04-30 Impact factor: 2.802
Authors: M A Alcántara; M T Villarreal; V Del Castillo; G Gutiérrez; Y Saldaña; I Maulen; R Lee; M Macías; L Orozco Journal: Clin Genet Date: 1999-05 Impact factor: 4.438
Authors: Carolyn H Buzin; Jinong Feng; Jin Yan; William Scaringe; Qiang Liu; Johan den Dunnen; Jerry R Mendell; Steve S Sommer Journal: Hum Mutat Date: 2005-02 Impact factor: 4.878
Authors: Gyula Acsadi; Steven A Moore; Angélique Chéron; Olivier Delalande; Lindsey Bennett; William Kupsky; Mohammad El-Baba; Elisabeth Le Rumeur; Jean-François Hubert Journal: J Biol Chem Date: 2012-03-27 Impact factor: 5.157
Authors: Payam Soltanzadeh; Michael J Friez; Diane Dunn; Andrew von Niederhausern; Olga L Gurvich; Kathryn J Swoboda; Jacinda B Sampson; Alan Pestronk; Anne M Connolly; Julaine M Florence; Richard S Finkel; Carsten G Bönnemann; Livija Medne; Jerry R Mendell; Katherine D Mathews; Brenda L Wong; Michael D Sussman; Jonathan Zonana; Karen Kovak; Sidney M Gospe; Eduard Gappmaier; Laura E Taylor; Michael T Howard; Robert B Weiss; Kevin M Flanigan Journal: Neuromuscul Disord Date: 2010-07-13 Impact factor: 4.296
Authors: Peter J Taylor; Grant A Betts; Sarah Maroulis; Christian Gilissen; Robyn L Pedersen; David R Mowat; Heather M Johnston; Michael F Buckley Journal: PLoS One Date: 2010-01-20 Impact factor: 3.240
Authors: Jeffrey R Guyon; Julie Goswami; Susan J Jun; Marielle Thorne; Melanie Howell; Timothy Pusack; Genri Kawahara; Leta S Steffen; Michal Galdzicki; Louis M Kunkel Journal: Hum Mol Genet Date: 2008-10-28 Impact factor: 6.150