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CHD7 mutation spectrum in 28 Swedish patients diagnosed with CHARGE syndrome

Wincent, J; Holmberg, E; Stromland, K; Soller, Maria LU ; Mirzaei, L; Djureinovic, T; Robinson, K L; Anderlid, B M and Schoumans, J (2008) In Clinical Genetics 74(1). p.31-38
Abstract
CHARGE syndrome is a disorder characterized by Coloboma, Heart defect, Atresia choanae, Retarded growth and/or development, Genital hypoplasia and Ear anomalies. Heterozygous mutations in the chromodomain helicase DNA-binding protein 7 (CHD7) gene have been identified in about 60% of individuals diagnosed with CHARGE syndrome. We performed a CHD7 mutation screening by direct exon sequencing in 28 index patients (26 sporadic cases, 1 familial case consisting of a brother and sister and 1 case consisting of monozygotic twins) diagnosed with CHARGE syndrome in order to determine the mutations in a cohort of Swedish CHARGE syndrome patients. The patients without a detectable CHD7 mutation, or with a missense mutation, were further investigated... (More)
CHARGE syndrome is a disorder characterized by Coloboma, Heart defect, Atresia choanae, Retarded growth and/or development, Genital hypoplasia and Ear anomalies. Heterozygous mutations in the chromodomain helicase DNA-binding protein 7 (CHD7) gene have been identified in about 60% of individuals diagnosed with CHARGE syndrome. We performed a CHD7 mutation screening by direct exon sequencing in 28 index patients (26 sporadic cases, 1 familial case consisting of a brother and sister and 1 case consisting of monozygotic twins) diagnosed with CHARGE syndrome in order to determine the mutations in a cohort of Swedish CHARGE syndrome patients. The patients without a detectable CHD7 mutation, or with a missense mutation, were further investigated by multiplex ligation-dependent probe amplification (MLPA) in order to search for intragenic deletions or duplications. Thirteen novel mutations and five previously reported mutations were detected. The mutations were scattered throughout the gene and included nonsense, frameshift and missense mutations as well as intragenic deletions. In conclusion, CHD7 mutations were detected in a large proportion (64%) of cases diagnosed with CHARGE syndrome. Screening for intragenic deletions with MLPA is recommended in cases where mutations are not found by sequencing. In addition, a CDH7 mutation was found in an individual without temporal bone malformation. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
MLPA, deletion, CHARGE syndrome, CHD7, mutation
in
Clinical Genetics
volume
74
issue
1
pages
31 - 38
publisher
Wiley-Blackwell
external identifiers
  • wos:000256720700004
  • scopus:45149091512
ISSN
0009-9163
DOI
10.1111/j.1399-0004.2008.01014.x
language
English
LU publication?
yes
id
4dd2eb0a-12b6-42d5-996a-486041a9f1a5 (old id 1191104)
alternative location
http://www3.interscience.wiley.com/cgi-bin/fulltext/120083842/HTMLSTART
date added to LUP
2008-09-08 11:30:36
date last changed
2017-01-22 03:24:06
@article{4dd2eb0a-12b6-42d5-996a-486041a9f1a5,
  abstract     = {CHARGE syndrome is a disorder characterized by Coloboma, Heart defect, Atresia choanae, Retarded growth and/or development, Genital hypoplasia and Ear anomalies. Heterozygous mutations in the chromodomain helicase DNA-binding protein 7 (CHD7) gene have been identified in about 60% of individuals diagnosed with CHARGE syndrome. We performed a CHD7 mutation screening by direct exon sequencing in 28 index patients (26 sporadic cases, 1 familial case consisting of a brother and sister and 1 case consisting of monozygotic twins) diagnosed with CHARGE syndrome in order to determine the mutations in a cohort of Swedish CHARGE syndrome patients. The patients without a detectable CHD7 mutation, or with a missense mutation, were further investigated by multiplex ligation-dependent probe amplification (MLPA) in order to search for intragenic deletions or duplications. Thirteen novel mutations and five previously reported mutations were detected. The mutations were scattered throughout the gene and included nonsense, frameshift and missense mutations as well as intragenic deletions. In conclusion, CHD7 mutations were detected in a large proportion (64%) of cases diagnosed with CHARGE syndrome. Screening for intragenic deletions with MLPA is recommended in cases where mutations are not found by sequencing. In addition, a CDH7 mutation was found in an individual without temporal bone malformation.},
  author       = {Wincent, J and Holmberg, E and Stromland, K and Soller, Maria and Mirzaei, L and Djureinovic, T and Robinson, K L and Anderlid, B M and Schoumans, J},
  issn         = {0009-9163},
  keyword      = {MLPA,deletion,CHARGE syndrome,CHD7,mutation},
  language     = {eng},
  number       = {1},
  pages        = {31--38},
  publisher    = {Wiley-Blackwell},
  series       = {Clinical Genetics},
  title        = {CHD7 mutation spectrum in 28 Swedish patients diagnosed with CHARGE syndrome},
  url          = {http://dx.doi.org/10.1111/j.1399-0004.2008.01014.x},
  volume       = {74},
  year         = {2008},
}