Identifying candidate genes underlying isolated congenital anosmia
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd..
An estimated 1 in 10 000 people are born without the ability to smell, a condition known as congenital anosmia, and about one third of those people have non-syndromic, or isolated congenital anosmia (ICA). Despite the significant impact of olfaction for our quality of life, the underlying causes of ICA remain largely unknown. Using whole exome sequencing (WES) in 10 families and 141 individuals with ICA, we identified a candidate list of 162 rare, segregating, deleterious variants in 158 genes. We confirmed the involvement of CNGA2, a previously implicated ICA gene that is an essential component of the olfactory transduction pathway. Furthermore, we found a loss-of-function variant in SREK1IP1 from the family gene candidate list, which was also observed in 5% of individuals in an additional non-family cohort with ICA. Although SREK1IP1 has not been previously associated with olfaction, its role in zinc ion binding suggests a potential influence on olfactory signaling. This study provides a more comprehensive understanding of the spectrum of genetic alterations and their etiology in ICA patients, which may improve the diagnosis, prognosis, and treatment of this disorder and lead to better understanding of the mechanisms governing basic olfactory function.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:105 |
|---|---|
| Enthalten in: |
Clinical genetics - 105(2024), 4 vom: 01. Apr., Seite 376-385 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kamarck, Marissa L [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Anosmia |
|---|
| Anmerkungen: |
Date Completed 07.03.2024 Date Revised 09.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/cge.14470 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM366392786 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM366392786 | ||
| 003 | DE-627 | ||
| 005 | 20240410232347.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231229s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/cge.14470 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1371.xml |
| 035 | |a (DE-627)NLM366392786 | ||
| 035 | |a (NLM)38148624 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kamarck, Marissa L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Identifying candidate genes underlying isolated congenital anosmia |
| 264 | 1 | |c 2024 | |
| 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 07.03.2024 | ||
| 500 | |a Date Revised 09.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. | ||
| 520 | |a An estimated 1 in 10 000 people are born without the ability to smell, a condition known as congenital anosmia, and about one third of those people have non-syndromic, or isolated congenital anosmia (ICA). Despite the significant impact of olfaction for our quality of life, the underlying causes of ICA remain largely unknown. Using whole exome sequencing (WES) in 10 families and 141 individuals with ICA, we identified a candidate list of 162 rare, segregating, deleterious variants in 158 genes. We confirmed the involvement of CNGA2, a previously implicated ICA gene that is an essential component of the olfactory transduction pathway. Furthermore, we found a loss-of-function variant in SREK1IP1 from the family gene candidate list, which was also observed in 5% of individuals in an additional non-family cohort with ICA. Although SREK1IP1 has not been previously associated with olfaction, its role in zinc ion binding suggests a potential influence on olfactory signaling. This study provides a more comprehensive understanding of the spectrum of genetic alterations and their etiology in ICA patients, which may improve the diagnosis, prognosis, and treatment of this disorder and lead to better understanding of the mechanisms governing basic olfactory function | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CNGA2 | |
| 650 | 4 | |a anosmia | |
| 650 | 4 | |a olfaction | |
| 650 | 4 | |a smell loss | |
| 650 | 7 | |a CNGA2 protein, human |2 NLM | |
| 650 | 7 | |a Cyclic Nucleotide-Gated Cation Channels |2 NLM | |
| 700 | 1 | |a Trimmer, Casey |e verfasserin |4 aut | |
| 700 | 1 | |a Murphy, Nicolle R |e verfasserin |4 aut | |
| 700 | 1 | |a Gregory, Kristen M |e verfasserin |4 aut | |
| 700 | 1 | |a Manoel, Diogo |e verfasserin |4 aut | |
| 700 | 1 | |a Logan, Darren W |e verfasserin |4 aut | |
| 700 | 1 | |a Saraiva, Luis R |e verfasserin |4 aut | |
| 700 | 1 | |a Mainland, Joel D |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Clinical genetics |d 1971 |g 105(2024), 4 vom: 01. Apr., Seite 376-385 |w (DE-627)NLM00004914X |x 1399-0004 |7 nnns |
| 773 | 1 | 8 | |g volume:105 |g year:2024 |g number:4 |g day:01 |g month:04 |g pages:376-385 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/cge.14470 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 105 |j 2024 |e 4 |b 01 |c 04 |h 376-385 | ||