Intragenic deletions in 21 Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) families studied with the dystrophin cDNA: Location of breakpoints on HindIII and BglII exon-containing fragment maps, meiotic and mitotic origin of the mutations

B. T. Darras, P. Blattner, J. F. Harper, A. J. Spiro, S. Alter, U. Francke

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Following the strategy outlined in an accompanying paper, we studied 32 X-linked muscular dystrophy families (29 Duchenne [DMD][ and three Becker [BMD] type) for abnormalities of HindIII and BglII fragments detected by the entire dystrophin cDNA. Twenty-one different single-intragenic deletions, and no duplications, were identified. The deletion endpoints were precisely mapped on the published HindIII fragment map. Detailed analysis of overlapping deletions led to clarification of the fragment order for some previously unsettled regions of the HindIII map and to the construction of a partial map of exon-containing BglII fragments. For the regions involved in deletions, the corresponding HindIII and BglIII fragments could be identified. Noncontiguous comigrating fragments were detected in two regions by careful analysis of the patterns in deletion patients. Four of the 21 deletions generated novel restriction fragments that facilitated detection of female carriers in these families. Twelve of the deletions had a breakpoint in one of the two large introns known to be the sites of breakpoint clusters. By combining deletions and RFLP analyses, we unequivocally identified the gamete that the first carried the mutation in 13 families: eight oocytes and five sperm. Germ-line mosaicism previously detected in one male was confirmed by cDNA studies. In two additional families gonadal mosaicism was found in females. As evidence is accumulating for frequent mitotic origin of these deletion mutations, this phenomenon has to be considered when postulating mutational mechanisms and in genetic counseling of DMD/BMD families.

Original languageEnglish (US)
Pages (from-to)620-629
Number of pages10
JournalAmerican Journal of Human Genetics
Volume43
Issue number5
StatePublished - 1988
Externally publishedYes

Fingerprint

Dystrophin
Duchenne Muscular Dystrophy
Exons
Complementary DNA
Mutation
Mosaicism
Germ Cells
Muscular Dystrophies
Sequence Deletion
Genetic Counseling
Restriction Fragment Length Polymorphisms
Introns
Oocytes
Spermatozoa

ASJC Scopus subject areas

  • Genetics

Cite this

@article{32b73c716764439f9fe8ea4b48ded057,
title = "Intragenic deletions in 21 Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) families studied with the dystrophin cDNA: Location of breakpoints on HindIII and BglII exon-containing fragment maps, meiotic and mitotic origin of the mutations",
abstract = "Following the strategy outlined in an accompanying paper, we studied 32 X-linked muscular dystrophy families (29 Duchenne [DMD][ and three Becker [BMD] type) for abnormalities of HindIII and BglII fragments detected by the entire dystrophin cDNA. Twenty-one different single-intragenic deletions, and no duplications, were identified. The deletion endpoints were precisely mapped on the published HindIII fragment map. Detailed analysis of overlapping deletions led to clarification of the fragment order for some previously unsettled regions of the HindIII map and to the construction of a partial map of exon-containing BglII fragments. For the regions involved in deletions, the corresponding HindIII and BglIII fragments could be identified. Noncontiguous comigrating fragments were detected in two regions by careful analysis of the patterns in deletion patients. Four of the 21 deletions generated novel restriction fragments that facilitated detection of female carriers in these families. Twelve of the deletions had a breakpoint in one of the two large introns known to be the sites of breakpoint clusters. By combining deletions and RFLP analyses, we unequivocally identified the gamete that the first carried the mutation in 13 families: eight oocytes and five sperm. Germ-line mosaicism previously detected in one male was confirmed by cDNA studies. In two additional families gonadal mosaicism was found in females. As evidence is accumulating for frequent mitotic origin of these deletion mutations, this phenomenon has to be considered when postulating mutational mechanisms and in genetic counseling of DMD/BMD families.",
author = "Darras, {B. T.} and P. Blattner and Harper, {J. F.} and Spiro, {A. J.} and S. Alter and U. Francke",
year = "1988",
language = "English (US)",
volume = "43",
pages = "620--629",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Intragenic deletions in 21 Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) families studied with the dystrophin cDNA

T2 - Location of breakpoints on HindIII and BglII exon-containing fragment maps, meiotic and mitotic origin of the mutations

AU - Darras, B. T.

AU - Blattner, P.

AU - Harper, J. F.

AU - Spiro, A. J.

AU - Alter, S.

AU - Francke, U.

PY - 1988

Y1 - 1988

N2 - Following the strategy outlined in an accompanying paper, we studied 32 X-linked muscular dystrophy families (29 Duchenne [DMD][ and three Becker [BMD] type) for abnormalities of HindIII and BglII fragments detected by the entire dystrophin cDNA. Twenty-one different single-intragenic deletions, and no duplications, were identified. The deletion endpoints were precisely mapped on the published HindIII fragment map. Detailed analysis of overlapping deletions led to clarification of the fragment order for some previously unsettled regions of the HindIII map and to the construction of a partial map of exon-containing BglII fragments. For the regions involved in deletions, the corresponding HindIII and BglIII fragments could be identified. Noncontiguous comigrating fragments were detected in two regions by careful analysis of the patterns in deletion patients. Four of the 21 deletions generated novel restriction fragments that facilitated detection of female carriers in these families. Twelve of the deletions had a breakpoint in one of the two large introns known to be the sites of breakpoint clusters. By combining deletions and RFLP analyses, we unequivocally identified the gamete that the first carried the mutation in 13 families: eight oocytes and five sperm. Germ-line mosaicism previously detected in one male was confirmed by cDNA studies. In two additional families gonadal mosaicism was found in females. As evidence is accumulating for frequent mitotic origin of these deletion mutations, this phenomenon has to be considered when postulating mutational mechanisms and in genetic counseling of DMD/BMD families.

AB - Following the strategy outlined in an accompanying paper, we studied 32 X-linked muscular dystrophy families (29 Duchenne [DMD][ and three Becker [BMD] type) for abnormalities of HindIII and BglII fragments detected by the entire dystrophin cDNA. Twenty-one different single-intragenic deletions, and no duplications, were identified. The deletion endpoints were precisely mapped on the published HindIII fragment map. Detailed analysis of overlapping deletions led to clarification of the fragment order for some previously unsettled regions of the HindIII map and to the construction of a partial map of exon-containing BglII fragments. For the regions involved in deletions, the corresponding HindIII and BglIII fragments could be identified. Noncontiguous comigrating fragments were detected in two regions by careful analysis of the patterns in deletion patients. Four of the 21 deletions generated novel restriction fragments that facilitated detection of female carriers in these families. Twelve of the deletions had a breakpoint in one of the two large introns known to be the sites of breakpoint clusters. By combining deletions and RFLP analyses, we unequivocally identified the gamete that the first carried the mutation in 13 families: eight oocytes and five sperm. Germ-line mosaicism previously detected in one male was confirmed by cDNA studies. In two additional families gonadal mosaicism was found in females. As evidence is accumulating for frequent mitotic origin of these deletion mutations, this phenomenon has to be considered when postulating mutational mechanisms and in genetic counseling of DMD/BMD families.

UR - http://www.scopus.com/inward/record.url?scp=0023745057&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023745057&partnerID=8YFLogxK

M3 - Article

C2 - 2903663

AN - SCOPUS:0023745057

VL - 43

SP - 620

EP - 629

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 5

ER -