Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Eight mutations including 5 novel ones in the COL1A1 gene in Czech patients with osteogenesis imperfecta

L. Hruskova, I. Fijalkowski, W. Van Hul, I. Marik, G. Mortier, P. Martasek, I. Mazura

. 2016 ; 160 (3) : 442-447. [pub] 20160427

Jazyk angličtina Země Česko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc17016669

BACKGROUND AND AIM: Osteogenesis imperfecta (OI), also called brittle bone disease, is a clinically and genetically heterogeneous disorder characterized by decreased bone density. Autosomal dominant forms result from mutations in either the COL1A1 (collagen type I alpha-1 chain) or COL1A2 (collagen type I alpha-2 chain) genes encoding the type I collagen. The aim of this study was to identify mutations and allelic variants of the COL1A1 gene in patients with osteogenesis imperfecta (OI). METHODS AND RESULTS: Molecular genetic analysis of the COL1A1 gene was performed in a cohort of 34 patients with OI. The DNA samples were analysed by PCR and Sanger sequencing. DNA changes in coding sequences of the gene were compared with Type 1 Collagen Mutation Database. Genetic variants resulting in either quantitatively or structurally defective protein production were found in 6 unrelated patients. Four identified mutations are connected to decreased protein production (Tyr47X, Arg131X, Arg415X, Gln1341X), 2 result in amino acid substitution (Cys61Phe, Pro1186Ala) and the last affects splicing (c.1057-1G>T). Further, one silent mutation (Gly794Gly) was detected. No protein analysis was performed. CONCLUSION: Of the 8 identified mutations, 5 were novel and have not been reported before. Only one causes substitution of glycine located within the Gly-X-Y triplets in the triple helical domain. Two mutations are located in major ligand binding regions (MLBR) which are important for bone strength and flexibility. Although the genotype-phenotype correlation is still unclear, our findings should contribute to elucidating this relationship in patients diagnosed with OI.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc17016669
003      
CZ-PrNML
005      
20170519133134.0
007      
ta
008      
170516s2016 xr d f 000 0|eng||
009      
AR
024    7_
$a 10.5507/bp.2016.022 $2 doi
035    __
$a (PubMed)27132807
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xr
100    1_
$a Hrušková, Lucie $u Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague, Czech Republic $7 xx0218035
245    10
$a Eight mutations including 5 novel ones in the COL1A1 gene in Czech patients with osteogenesis imperfecta / $c L. Hruskova, I. Fijalkowski, W. Van Hul, I. Marik, G. Mortier, P. Martasek, I. Mazura
520    9_
$a BACKGROUND AND AIM: Osteogenesis imperfecta (OI), also called brittle bone disease, is a clinically and genetically heterogeneous disorder characterized by decreased bone density. Autosomal dominant forms result from mutations in either the COL1A1 (collagen type I alpha-1 chain) or COL1A2 (collagen type I alpha-2 chain) genes encoding the type I collagen. The aim of this study was to identify mutations and allelic variants of the COL1A1 gene in patients with osteogenesis imperfecta (OI). METHODS AND RESULTS: Molecular genetic analysis of the COL1A1 gene was performed in a cohort of 34 patients with OI. The DNA samples were analysed by PCR and Sanger sequencing. DNA changes in coding sequences of the gene were compared with Type 1 Collagen Mutation Database. Genetic variants resulting in either quantitatively or structurally defective protein production were found in 6 unrelated patients. Four identified mutations are connected to decreased protein production (Tyr47X, Arg131X, Arg415X, Gln1341X), 2 result in amino acid substitution (Cys61Phe, Pro1186Ala) and the last affects splicing (c.1057-1G>T). Further, one silent mutation (Gly794Gly) was detected. No protein analysis was performed. CONCLUSION: Of the 8 identified mutations, 5 were novel and have not been reported before. Only one causes substitution of glycine located within the Gly-X-Y triplets in the triple helical domain. Two mutations are located in major ligand binding regions (MLBR) which are important for bone strength and flexibility. Although the genotype-phenotype correlation is still unclear, our findings should contribute to elucidating this relationship in patients diagnosed with OI.
650    _2
$a mladiství $7 D000293
650    _2
$a dospělí $7 D000328
650    _2
$a substituce aminokyselin $x genetika $7 D019943
650    _2
$a dítě $7 D002648
650    _2
$a kolagen typu I $x genetika $7 D024042
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a genotyp $7 D005838
650    _2
$a glycin $x genetika $7 D005998
650    _2
$a heterozygot $7 D006579
650    _2
$a lidé $7 D006801
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    _2
$a mutace $x genetika $7 D009154
650    _2
$a osteogenesis imperfecta $x genetika $7 D010013
650    _2
$a fenotyp $7 D010641
650    _2
$a mladý dospělý $7 D055815
655    _2
$a časopisecké články $7 D016428
700    1_
$a Fijalkowski, Igor $u Centre of Medical Genetics, Antwerp University and University Hospital, Antwerp, Belgium
700    1_
$a Van Hul, Wim $u Centre of Medical Genetics, Antwerp University and University Hospital, Antwerp, Belgium
700    1_
$a Mařík, I., $u Ambulant Centre for Defects of Locomotor Apparatus 1.1.c., Prague, Czech Republic; Faculty of Medical Studies, West Bohemia University, Pilsen, Czech Republic $d 1950- $7 skuk0003963
700    1_
$a Mortier, Geert $u Centre of Medical Genetics, Antwerp University and University Hospital, Antwerp, Belgium
700    1_
$a Martásek, Pavel, $u Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague, Czech Republic $d 1952- $7 xx0077949
700    1_
$a Mazura, Ivan $u Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague, Czech Republic
773    0_
$w MED00012606 $t Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czech Republic $x 1213-8118 $g Roč. 160, č. 3 (2016), s. 442-447
910    __
$a ABA008 $b A 1502 $c 958 $y 4 $z 0
990    __
$a 20170516 $b ABA008
991    __
$a 20170518101405 $b ABA008
999    __
$a ok $b bmc $g 1205815 $s 977478
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2016 $b 160 $c 3 $d 442-447 $e 20160427 $i 1213-8118 $m Biomedical papers of the Medical Faculty of the University Palacký, Olomouc Czech Republic $n Biomed. Pap. Fac. Med. Palacký Univ. Olomouc Czech Repub. (Print) $x MED00012606
LZP    __
$b NLK118 $a Pubmed-20170516

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace