Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Disease-Causing TIMP3 Variants and Deep Phenotyping of Two Czech Families with Sorsby Fundus Dystrophy Associated with Novel p.(Tyr152Cys) Mutation

A. Vergaro, M. Pankievic, J. Jedlickova, L. Dudakova, M. Vajter, M. Michaelides, M. Meliska, P. Nemec, D. Babincova, B. Kousal, P. Liskova

. 2024 ; 25 (7) : . [pub] 20240327

Language English Country Switzerland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc24014537

Grant support
099173/Z/12/Z Wellcome Trust - United Kingdom

We aim to report the ocular phenotype and molecular genetic findings in two Czech families with Sorsby fundus dystrophy and to review all the reported TIMP3 pathogenic variants. Two probands with Sorsby fundus dystrophy and three first-degree relatives underwent ocular examination and retinal imaging, including optical coherence tomography angiography. The DNA of the first proband was screened using a targeted ocular gene panel, while, in the second proband, direct sequencing of the TIMP3 coding region was performed. Sanger sequencing was also used for segregation analysis within the families. All the previously reported TIMP3 variants were reviewed using the American College of Medical Genetics and the Association for Molecular Pathology interpretation framework. A novel heterozygous variant, c.455A>G p.(Tyr152Cys), in TIMP3 was identified in both families and potentially de novo in one. Optical coherence tomography angiography documented in one patient the development of a choroidal neovascular membrane at 54 years. Including this study, 23 heterozygous variants in TIMP3 have been reported as disease-causing. Application of gene-specific criteria denoted eleven variants as pathogenic, eleven as likely pathogenic, and one as a variant of unknown significance. Our study expands the spectrum of TIMP3 pathogenic variants and highlights the importance of optical coherence tomography angiography for early detection of choroidal neovascular membranes.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24014537
003      
CZ-PrNML
005      
20240905134132.0
007      
ta
008      
240725s2024 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/ijms25073744 $2 doi
035    __
$a (PubMed)38612555
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Vergaro, Andrea $u Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic $u Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic
245    10
$a Disease-Causing TIMP3 Variants and Deep Phenotyping of Two Czech Families with Sorsby Fundus Dystrophy Associated with Novel p.(Tyr152Cys) Mutation / $c A. Vergaro, M. Pankievic, J. Jedlickova, L. Dudakova, M. Vajter, M. Michaelides, M. Meliska, P. Nemec, D. Babincova, B. Kousal, P. Liskova
520    9_
$a We aim to report the ocular phenotype and molecular genetic findings in two Czech families with Sorsby fundus dystrophy and to review all the reported TIMP3 pathogenic variants. Two probands with Sorsby fundus dystrophy and three first-degree relatives underwent ocular examination and retinal imaging, including optical coherence tomography angiography. The DNA of the first proband was screened using a targeted ocular gene panel, while, in the second proband, direct sequencing of the TIMP3 coding region was performed. Sanger sequencing was also used for segregation analysis within the families. All the previously reported TIMP3 variants were reviewed using the American College of Medical Genetics and the Association for Molecular Pathology interpretation framework. A novel heterozygous variant, c.455A>G p.(Tyr152Cys), in TIMP3 was identified in both families and potentially de novo in one. Optical coherence tomography angiography documented in one patient the development of a choroidal neovascular membrane at 54 years. Including this study, 23 heterozygous variants in TIMP3 have been reported as disease-causing. Application of gene-specific criteria denoted eleven variants as pathogenic, eleven as likely pathogenic, and one as a variant of unknown significance. Our study expands the spectrum of TIMP3 pathogenic variants and highlights the importance of optical coherence tomography angiography for early detection of choroidal neovascular membranes.
650    _2
$a lidé $7 D006801
650    12
$a makulární degenerace $7 D008268
650    _2
$a oči $7 D005123
650    _2
$a mutace $7 D009154
650    12
$a neovaskularizace choroidey $7 D020256
650    _2
$a tkáňový inhibitor metaloproteinasy 3 $x genetika $7 D019717
651    _2
$a Česká republika $7 D018153
655    _2
$a časopisecké články $7 D016428
700    1_
$a Pankievic, Monika $u Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic
700    1_
$a Jedlickova, Jana $u Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic $1 https://orcid.org/0000000217691659
700    1_
$a Dudakova, Lubica $u Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic $1 https://orcid.org/0000000347188955 $7 xx0241088
700    1_
$a Vajter, Marie $u Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic $u Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic $1 https://orcid.org/0000000295909633
700    1_
$a Michaelides, Michel $u UCL Institute of Ophthalmology, University College London and Moorfields Eye Hospital, London EC1V 9EL, UK
700    1_
$a Meliska, Martin $u Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic
700    1_
$a Nemec, Pavel $u Department of Ophthalmology, First Faculty of Medicine and Military University Hospital Prague, 162 00 Prague, Czech Republic
700    1_
$a Babincova, Daniela $u Laboratory of Molecular Biology, AGEL, 741 01 Nový Jíčín, Czech Republic $1 https://orcid.org/0009000594599695
700    1_
$a Kousal, Bohdan $u Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic $1 https://orcid.org/0000000328242266 $7 xx0173360
700    1_
$a Liskova, Petra $u Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic $u Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic $1 https://orcid.org/0000000178348486 $7 xx0173361
773    0_
$w MED00176142 $t International journal of molecular sciences $x 1422-0067 $g Roč. 25, č. 7 (2024)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/38612555 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20240725 $b ABA008
991    __
$a 20240905134126 $b ABA008
999    __
$a ok $b bmc $g 2143976 $s 1226403
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 25 $c 7 $e 20240327 $i 1422-0067 $m International journal of molecular sciences $n Int J Mol Sci $x MED00176142
GRA    __
$a 099173/Z/12/Z $p Wellcome Trust $2 United Kingdom
LZP    __
$a Pubmed-20240725

Find record

Citation metrics

Archiving options