The aim of this study was to identify RS1 pathogenic variants in Czech patients with X-linked retinoschisis (XLRS) and to describe the associated phenotypes, including natural history, in some cases. Twenty-one affected males from 17 families were included. The coding region of RS1 was directly sequenced and segregation of the identified mutations was performed in available family members. In total, 12 disease-causing variants within RS1 were identified; of these c.20del, c.275G>A, c.[375_379del; 386A>T], c.539C>A and c.575_576insT were novel, all predicted to be null alleles. The c.539C>A mutation occurred de novo. Three patients (aged 8, 11 and 19 years) were misdiagnosed as having intermediate uveitis and treated with systemic steroids. Repeat spectral domain optical coherence tomography examinations in four eyes documented the transition from cystoid macular lesions to macular atrophy in the fourth decade of life. Four individuals were treated with topical dorzolamide and in two of them, complete resolution of the cystic macular lesions bilaterally was achieved, while one patient was noncompliant. Rebound phenomenon after discontinuation of dorzolamide for 7 days was documented in one case. Misdiagnosis of XLRS for uveitis is not uncommon; therefore, identification of disease-causing variants is of considerable benefit to the affected individuals.

Department of Ophthalmology 1st Faculty of Medicine Charles University and General University Hospital Prague 128 08 Prague Czech Republic

Department of Ophthalmology Faculty of Medicine in Hradec Kralove Charles University and University Hospital Hradec Kralove 500 05 Hradec Kralove Czech Republic

Department of Ophthalmology New Zealand National Eye Centre University of Auckland Auckland 1142 New Zealand

Department of Paediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital Prague 128 08 Prague Czech Republic

000      

00000naa a2200000 a 4500

001      

bmc22011915

003      

CZ-PrNML

005      

20220506130841.0

007      

ta

008      

220425s2021 sz f 000 0|eng||

009      

AR

024    7_

$a 10.3390/genes12111816 $2 doi

035    __

$a (PubMed)34828422

040    __

$a ABA008 $b cze $d ABA008 $e AACR2

041    0_

$a eng

044    __

$a sz

100    1_

$a Kousal, Bohdan $u Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 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 Clinical and Genetic Study of X-Linked Juvenile Retinoschisis in the Czech Population / $c B. Kousal, L. Hlavata, H. Vlaskova, L. Dvorakova, M. Brichova, Z. Dubska, H. Langrova, AL. Vincent, L. Dudakova, P. Liskova

520    9_

$a The aim of this study was to identify RS1 pathogenic variants in Czech patients with X-linked retinoschisis (XLRS) and to describe the associated phenotypes, including natural history, in some cases. Twenty-one affected males from 17 families were included. The coding region of RS1 was directly sequenced and segregation of the identified mutations was performed in available family members. In total, 12 disease-causing variants within RS1 were identified; of these c.20del, c.275G>A, c.[375_379del; 386A>T], c.539C>A and c.575_576insT were novel, all predicted to be null alleles. The c.539C>A mutation occurred de novo. Three patients (aged 8, 11 and 19 years) were misdiagnosed as having intermediate uveitis and treated with systemic steroids. Repeat spectral domain optical coherence tomography examinations in four eyes documented the transition from cystoid macular lesions to macular atrophy in the fourth decade of life. Four individuals were treated with topical dorzolamide and in two of them, complete resolution of the cystic macular lesions bilaterally was achieved, while one patient was noncompliant. Rebound phenomenon after discontinuation of dorzolamide for 7 days was documented in one case. Misdiagnosis of XLRS for uveitis is not uncommon; therefore, identification of disease-causing variants is of considerable benefit to the affected individuals.

650    _2

$a mladiství $7 D000293

650    _2

$a antihypertenziva $x aplikace a dávkování $x terapeutické užití $7 D000959

650    _2

$a dítě $7 D002648

650    _2

$a předškolní dítě $7 D002675

650    _2

$a oční proteiny $x genetika $7 D005136

650    _2

$a frekvence genu $7 D005787

650    _2

$a lidé $7 D006801

650    _2

$a kojenec $7 D007223

650    _2

$a mutace $7 D009154

650    _2

$a rodokmen $7 D010375

650    _2

$a retinoschisis $x farmakoterapie $x genetika $x patologie $7 D041441

650    _2

$a sulfonamidy $x aplikace a dávkování $x terapeutické užití $7 D013449

650    _2

$a thiofeny $x aplikace a dávkování $x terapeutické užití $7 D013876

650    _2

$a optická koherentní tomografie $7 D041623

651    _2

$a Česká republika $7 D018153

655    _2

$a časopisecké články $7 D016428

655    _2

$a práce podpořená grantem $7 D013485

700    1_

$a Hlavata, Lucia $u Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic

700    1_

$a Vlaskova, Hana $u Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic

700    1_

$a Dvorakova, Lenka $u Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic

700    1_

$a Brichova, Michaela $u Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic

700    1_

$a Dubska, Zora $u Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic

700    1_

$a Langrova, Hana $u Department of Ophthalmology, Faculty of Medicine in Hradec Kralove, Charles University and University Hospital Hradec Kralove, 500 05 Hradec Kralove, Czech Republic

700    1_

$a Vincent, Andrea L $u Department of Ophthalmology, New Zealand National Eye Centre, University of Auckland, Auckland 1142, New Zealand

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, 128 08 Prague, Czech Republic

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, 128 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

773    0_

$w MED00174652 $t Genes $x 2073-4425 $g Roč. 12, č. 11 (2021)

856    41

$u https://pubmed.ncbi.nlm.nih.gov/34828422 $y Pubmed

910    __

$a ABA008 $b sig $c sign $y p $z 0

990    __

$a 20220425 $b ABA008

991    __

$a 20220506130833 $b ABA008

999    __

$a ok $b bmc $g 1789492 $s 1163116

BAS    __

$a 3

BAS    __

$a PreBMC

BMC    __

$a 2021 $b 12 $c 11 $e 20211118 $i 2073-4425 $m Genes $n Genes (Basel) $x MED00174652

LZP    __

$a Pubmed-20220425