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

First Application of Whole Genome Sequencing in Myelinated Retinal Nerve Fibers (MRNF)

E. Scott Sills, C. Harrity, HI. Chu, JW. Wang, SH. Wood, SL. Tan

. 2024 ; 73 (4) : 665-670. [pub] 20240831

Status minimální Jazyk angličtina Země Česko

Typ dokumentu časopisecké články, kazuistiky

Perzistentní odkaz   https://www.medvik.cz/link/bmc24017598

Genetic features are currently unknown in myelinated retinal nerve fibers (MRNF). For a 20-year-old asymptomatic female with unilateral MRNF, we performed whole genome sequencing (WGS) by standard workflow protocol to produce contiguous long-read sequences with Illumina DNA PCR-Free Prep. After tagmentation, libraries were sequenced on separate runs via NovaSeq 6000 platform at 2 x 150bp read length. Gene variants included rs2248799, rs2672589, rs7555070, rs247616_T and rs2043085_C all associated with an increased macular degeneration risk, and seven novel variants of uncertain significance. For optic disc enlargement, variants rs9988687_A, rs11079419_T, rs6787363 and rs10862708_A suggested an increased risk for this condition. In contrast, modeling revealed retinal detachment risk was reduced by variants identified at rs9651980_T, rs4373767_T, and rs7940691_T which were among five other previously unreported variants. WGS data placed proband at the 66th and 64th percentiles for disc anomaly and retinal detachment risk, respectively. Additionally, risk determined from 16 loci associated with age-related macular degeneration found the patient to be at the 18th percentile for this diagnosis (i.e., below average genetic predisposition). Fundoscopic findings showed mean RNFL thickness was lower with MRNF (77 OS vs. 96?m OD) and RNFL symmetry was impaired (43 %) but stable between 2020 and 2023. Rim area and cup volume were also substantially different (2.33 OS vs. 1.34mm2 OD, and 0.001 OS vs. 0.151mm3 OD, respectively). As the first known evaluation of MRNF via WGS, these data reveal a mixed picture with variants associated with different risks for potentially related ocular pathologies. In addition, we identify multiple new variants of unknown significance. Factors affecting gene expression in MRNF require further study. Key words: Whole genome sequencing, Retina, Myelination, Anatomy, Gene variants.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24017598
003      
CZ-PrNML
005      
20250312151318.0
007      
ta
008      
241004s2024 xr f 000 0|eng||
009      
AR
024    7_
$a 10.33549/physiolres.935301 $2 doi
035    __
$a (PubMed)39264086
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xr
100    1_
$a Scott Sills, E $u Center for Advanced Genetics, Regenerative Biology Group, San Clemente, USA
245    10
$a First Application of Whole Genome Sequencing in Myelinated Retinal Nerve Fibers (MRNF) / $c E. Scott Sills, C. Harrity, HI. Chu, JW. Wang, SH. Wood, SL. Tan
520    9_
$a Genetic features are currently unknown in myelinated retinal nerve fibers (MRNF). For a 20-year-old asymptomatic female with unilateral MRNF, we performed whole genome sequencing (WGS) by standard workflow protocol to produce contiguous long-read sequences with Illumina DNA PCR-Free Prep. After tagmentation, libraries were sequenced on separate runs via NovaSeq 6000 platform at 2 x 150bp read length. Gene variants included rs2248799, rs2672589, rs7555070, rs247616_T and rs2043085_C all associated with an increased macular degeneration risk, and seven novel variants of uncertain significance. For optic disc enlargement, variants rs9988687_A, rs11079419_T, rs6787363 and rs10862708_A suggested an increased risk for this condition. In contrast, modeling revealed retinal detachment risk was reduced by variants identified at rs9651980_T, rs4373767_T, and rs7940691_T which were among five other previously unreported variants. WGS data placed proband at the 66th and 64th percentiles for disc anomaly and retinal detachment risk, respectively. Additionally, risk determined from 16 loci associated with age-related macular degeneration found the patient to be at the 18th percentile for this diagnosis (i.e., below average genetic predisposition). Fundoscopic findings showed mean RNFL thickness was lower with MRNF (77 OS vs. 96?m OD) and RNFL symmetry was impaired (43 %) but stable between 2020 and 2023. Rim area and cup volume were also substantially different (2.33 OS vs. 1.34mm2 OD, and 0.001 OS vs. 0.151mm3 OD, respectively). As the first known evaluation of MRNF via WGS, these data reveal a mixed picture with variants associated with different risks for potentially related ocular pathologies. In addition, we identify multiple new variants of unknown significance. Factors affecting gene expression in MRNF require further study. Key words: Whole genome sequencing, Retina, Myelination, Anatomy, Gene variants.
650    _2
$a lidé $7 D006801
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a mladý dospělý $7 D055815
650    12
$a sekvenování celého genomu $7 D000073336
650    12
$a nervová vlákna myelinizovaná $x patologie $7 D009413
650    _2
$a retina $x patologie $7 D012160
650    _2
$a genetická predispozice k nemoci $7 D020022
655    _2
$a časopisecké články $7 D016428
655    _2
$a kazuistiky $7 D002363
700    1_
$a Harrity, C
700    1_
$a Chu, H I
700    1_
$a Wang, J W
700    1_
$a Wood, S H
700    1_
$a Tan, S L
773    0_
$w MED00003824 $t Physiological research $x 1802-9973 $g Roč. 73, č. 4 (2024), s. 665-670
856    41
$u https://pubmed.ncbi.nlm.nih.gov/39264086 $y Pubmed
910    __
$a ABA008 $b A 4120 $c 266 $y - $z 0
990    __
$a 20241004 $b ABA008
991    __
$a 20250312151325 $b ABA008
999    __
$a min $b bmc $g 2283510 $s 1229548
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 73 $c 4 $d 665-670 $e 20240831 $i 1802-9973 $m Physiological research $n Physiol Res $x MED00003824
LZP    __
$a Pubmed-20241004

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...