• Something wrong with this record ?

Clinical-genetic analysis of selected genes involved in the development of the human skeleton in 128 Czech patients with suspected congenital skeletal abnormalities

Z. Spurná, P. Čapková, L. Punová, J. DuchoslavovÁ, D. Aleksijevic, P. Venháčová, J. Srovnal, J. Štellmachová, V. Curtisová, V. Bitnerová, J. Petřková, K. Kolaříková, M. Janíková, R. Kratochvílová, P. Vrtěl, R. Vodička, R. Vrtěl, J. Zapletalová

. 2024 ; 892 (-) : 147881. [pub] 20231006

Language English Country Netherlands

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc24000078

BACKGROUND: Congenital skeletal abnormalities are a heterogeneous group of diseases most commonly associated with small or disproportionate growth, cranial and facial dysmorphisms, delayed bone maturation, etc. Nonetheless, no detailed genotype-phenotype correlation in patients with specific genetic variants is readily available. Ergo, this study focuses on the analysis of patient phenotypes with candidate variants in genes involved in bone growth as detected by molecular genetic analysis. METHODS: In this study we used molecular genetic methods to analyse the ACAN, COL2A1, FGFR3, IGFALS, IGF1, IGF1R, GHR, NPR2, STAT5B and SHOX genes in 128 Czech children with suspected congenital skeletal abnormalities. Pathogenic variants and variants of unclear clinical significance were identified and we compared their frequency in this study cohort to the European non-Finnish population. Furthermore, a prediction tool was utilised to determine their possible impact on the final protein. All clinical patient data was obtained during pre-test genetic counselling. RESULTS: Pathogenic variants were identified in the FGFR3, GHR, COL2A1 and SHOX genes in a total of six patients. Furthermore, we identified 23 variants with unclear clinical significance and high allelic frequency in this cohort of patients with skeletal abnormalities. Five of them have not yet been reported in the scientific literature. CONCLUSION: Congenital skeletal abnormalities may lead to a number of musculoskeletal, neurological, cardiovascular problems. Knowledge of specific pathogenic variants may help us in therapeutic procedures.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24000078
003      
CZ-PrNML
005      
20240312105950.0
007      
ta
008      
240109e20231006ne f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.gene.2023.147881 $2 doi
035    __
$a (PubMed)37806643
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ne
100    1_
$a Spurná, Z $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic; Institute of Medical Genetics, Palacký University in Olomouc, Olomouc, Czech Republic
245    10
$a Clinical-genetic analysis of selected genes involved in the development of the human skeleton in 128 Czech patients with suspected congenital skeletal abnormalities / $c Z. Spurná, P. Čapková, L. Punová, J. DuchoslavovÁ, D. Aleksijevic, P. Venháčová, J. Srovnal, J. Štellmachová, V. Curtisová, V. Bitnerová, J. Petřková, K. Kolaříková, M. Janíková, R. Kratochvílová, P. Vrtěl, R. Vodička, R. Vrtěl, J. Zapletalová
520    9_
$a BACKGROUND: Congenital skeletal abnormalities are a heterogeneous group of diseases most commonly associated with small or disproportionate growth, cranial and facial dysmorphisms, delayed bone maturation, etc. Nonetheless, no detailed genotype-phenotype correlation in patients with specific genetic variants is readily available. Ergo, this study focuses on the analysis of patient phenotypes with candidate variants in genes involved in bone growth as detected by molecular genetic analysis. METHODS: In this study we used molecular genetic methods to analyse the ACAN, COL2A1, FGFR3, IGFALS, IGF1, IGF1R, GHR, NPR2, STAT5B and SHOX genes in 128 Czech children with suspected congenital skeletal abnormalities. Pathogenic variants and variants of unclear clinical significance were identified and we compared their frequency in this study cohort to the European non-Finnish population. Furthermore, a prediction tool was utilised to determine their possible impact on the final protein. All clinical patient data was obtained during pre-test genetic counselling. RESULTS: Pathogenic variants were identified in the FGFR3, GHR, COL2A1 and SHOX genes in a total of six patients. Furthermore, we identified 23 variants with unclear clinical significance and high allelic frequency in this cohort of patients with skeletal abnormalities. Five of them have not yet been reported in the scientific literature. CONCLUSION: Congenital skeletal abnormalities may lead to a number of musculoskeletal, neurological, cardiovascular problems. Knowledge of specific pathogenic variants may help us in therapeutic procedures.
650    _2
$a dítě $7 D002648
650    _2
$a lidé $7 D006801
650    12
$a poruchy růstu $x epidemiologie $x genetika $x metabolismus $7 D006130
650    _2
$a genetické asociační studie $7 D056726
650    _2
$a frekvence genu $x genetika $7 D005787
650    12
$a kostra $x metabolismus $7 D012863
650    _2
$a protein SHOX $x genetika $7 D000074122
651    _2
$a Česká republika $7 D018153
655    _2
$a časopisecké články $7 D016428
700    1_
$a Čapková, P $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic; Institute of Medical Genetics, Palacký University in Olomouc, Olomouc, Czech Republic. Electronic address: Pavlina.Capkova@fnol.cz
700    1_
$a Punová, L $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic; Institute of Medical Genetics, Palacký University in Olomouc, Olomouc, Czech Republic
700    1_
$a DuchoslavovÁ, J $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic; Institute of Medical Genetics, Palacký University in Olomouc, Olomouc, Czech Republic
700    1_
$a Aleksijevic, D $u Paediatrics Department, Palacký University and University Hospital, Olomouc, Czech Republic
700    1_
$a Venháčová, P $u Paediatrics Department, Palacký University and University Hospital, Olomouc, Czech Republic
700    1_
$a Srovnal, J $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic; Institute of Medical Genetics, Palacký University in Olomouc, Olomouc, Czech Republic; Institute of Molecular and Translational Medicine, Czech Advanced Technology and Research Institute, Palacky University in Olomouc, Czech Republic; Cancer Research Czech Republic, Olomouc, Czech Republic
700    1_
$a Štellmachová, J $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic; Institute of Medical Genetics, Palacký University in Olomouc, Olomouc, Czech Republic
700    1_
$a Curtisová, V $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic; Institute of Medical Genetics, Palacký University in Olomouc, Olomouc, Czech Republic
700    1_
$a Bitnerová, Veronika $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic; Institute of Medical Genetics, Palacký University in Olomouc, Olomouc, Czech Republic $7 xx0314714
700    1_
$a Petřková, J $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic; First Department of Internal Medicine - Cardiology, University Hospital Olomouc, Olomouc, Czech Republic; First Department of Internal Medicine - Cardiology, Palacký University in Olomouc, Olomouc, Czech Republic; Institute of Pathological Physiology, Palacký University in Olomouc, Olomouc, Czech Republic
700    1_
$a Kolaříková, K $u Department of Neurology, University Hospital Olomouc, Czech Republic; Department of Neurology, Palacky University Olomouc, Czech Republic
700    1_
$a Janíková, M $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic; Institute of Medical Genetics, Palacký University in Olomouc, Olomouc, Czech Republic; Institute of Clinical and Molecular Pathology, Palacký University in Olomouc, Olomouc, Czech Republic
700    1_
$a Kratochvílová, R $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic
700    1_
$a Vrtěl, P $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic; Institute of Medical Genetics, Palacký University in Olomouc, Olomouc, Czech Republic
700    1_
$a Vodička, R $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic; Institute of Medical Genetics, Palacký University in Olomouc, Olomouc, Czech Republic
700    1_
$a Vrtěl, R $u Institute of Medical Genetics, Olomouc University Hospital, Olomouc, Czech Republic; Institute of Medical Genetics, Palacký University in Olomouc, Olomouc, Czech Republic
700    1_
$a Zapletalová, J $u Paediatrics Department, Palacký University and University Hospital, Olomouc, Czech Republic
773    0_
$w MED00001888 $t Gene $x 1879-0038 $g Roč. 892 (20231006), s. 147881
856    41
$u https://pubmed.ncbi.nlm.nih.gov/37806643 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20240109 $b ABA008
991    __
$a 20240312105946 $b ABA008
999    __
$a ok $b bmc $g 2049029 $s 1209772
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 892 $c - $d 147881 $e 20231006 $i 1879-0038 $m Gene $n Gene $x MED00001888
LZP    __
$a Pubmed-20240109

Find record

Citation metrics

Archiving options