Compound heterozygous splice site variants in the SCLT1 gene highlight an additional candidate locus for Senior-Løken syndrome
Senior Løken syndrome (SLS) is a heterogeneous disorder characterized by severe retinal degenerations and juvenile-onset nephronophthisis. Genetic variants in ten different genes have been reported as the causes of SLS. Clinical evaluation of a patient with SLS and her unaffected parents revealed that the patient had infantile-onset retinal dystrophy and juvenile-onset nephronophthisis. Other systemic abnormalities included hepatic dysfunction, megacystis, mild learning disability, autism, obesity, and hyperinsulinemia. Whole-exome sequencing identified compound heterozygous SCLT1 variants (c.1218 + 3insT and c.1631A > G) in the patient. The unaffected parents were heterozygous for each variant. Transcript analysis using reverse transcription PCR demonstrated that the c.1218 + 3insT variant leads to exon 14 skipping (p.V383_M406del), while the other variant (c.1631A > G) primarily leads to exon 17 skipping (p.D480EfsX11) as well as minor amounts of two transcripts (6 bps deletion in the last of exon 17 [p.V543_K544del] and exons 17 and 18 skipping [p.D480E, S481_K610del]). Immunohistochemical analysis demonstrated that the Sclt1 protein was localized to the distal appendage of the photoreceptor basal body, indicating a ciliary protein. In conclusion, we identified compound heterozygous splice site variants of SCLT1 in a patient with a new form of ciliopathies that exhibits clinical features of SLS.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
Scientific reports - 8(2018), 1 vom: 13. Nov., Seite 16733 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Katagiri, Satoshi [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Case Reports |
|---|
| Anmerkungen: |
Date Completed 01.11.2019 Date Revised 13.11.2019 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41598-018-35152-6 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM290576326 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM290576326 | ||
| 003 | DE-627 | ||
| 005 | 20231226195612.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41598-018-35152-6 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0968.xml |
| 035 | |a (DE-627)NLM290576326 | ||
| 035 | |a (NLM)30425282 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Katagiri, Satoshi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Compound heterozygous splice site variants in the SCLT1 gene highlight an additional candidate locus for Senior-Løken syndrome |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.11.2019 | ||
| 500 | |a Date Revised 13.11.2019 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Senior Løken syndrome (SLS) is a heterogeneous disorder characterized by severe retinal degenerations and juvenile-onset nephronophthisis. Genetic variants in ten different genes have been reported as the causes of SLS. Clinical evaluation of a patient with SLS and her unaffected parents revealed that the patient had infantile-onset retinal dystrophy and juvenile-onset nephronophthisis. Other systemic abnormalities included hepatic dysfunction, megacystis, mild learning disability, autism, obesity, and hyperinsulinemia. Whole-exome sequencing identified compound heterozygous SCLT1 variants (c.1218 + 3insT and c.1631A > G) in the patient. The unaffected parents were heterozygous for each variant. Transcript analysis using reverse transcription PCR demonstrated that the c.1218 + 3insT variant leads to exon 14 skipping (p.V383_M406del), while the other variant (c.1631A > G) primarily leads to exon 17 skipping (p.D480EfsX11) as well as minor amounts of two transcripts (6 bps deletion in the last of exon 17 [p.V543_K544del] and exons 17 and 18 skipping [p.D480E, S481_K610del]). Immunohistochemical analysis demonstrated that the Sclt1 protein was localized to the distal appendage of the photoreceptor basal body, indicating a ciliary protein. In conclusion, we identified compound heterozygous splice site variants of SCLT1 in a patient with a new form of ciliopathies that exhibits clinical features of SLS | ||
| 650 | 4 | |a Case Reports | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a RNA Splice Sites |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a SCLT1 protein, human |2 NLM | |
| 650 | 7 | |a Sodium Channels |2 NLM | |
| 700 | 1 | |a Hayashi, Takaaki |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshitake, Kazutoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Murai, Noriyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Matsui, Zenichi |e verfasserin |4 aut | |
| 700 | 1 | |a Kubo, Hiroyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Satoh, Hiroyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Matsufuji, Senya |e verfasserin |4 aut | |
| 700 | 1 | |a Takamura, Tsuyoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Yokoo, Takashi |e verfasserin |4 aut | |
| 700 | 1 | |a Omori, Yoshihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Furukawa, Takahisa |e verfasserin |4 aut | |
| 700 | 1 | |a Iwata, Takeshi |e verfasserin |4 aut | |
| 700 | 1 | |a Nakano, Tadashi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Scientific reports |d 2011 |g 8(2018), 1 vom: 13. Nov., Seite 16733 |w (DE-627)NLM215703936 |x 2045-2322 |7 nnns |
| 773 | 1 | 8 | |g volume:8 |g year:2018 |g number:1 |g day:13 |g month:11 |g pages:16733 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41598-018-35152-6 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 8 |j 2018 |e 1 |b 13 |c 11 |h 16733 | ||