A Recessively Inherited Risk Locus on Chromosome 13q22-31 Conferring Susceptibility to Schizophrenia
© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center..
We report a consanguineous family in which schizophrenia segregates in a manner consistent with recessive inheritance of a rare, partial-penetrance susceptibility allele. From 4 marriages between 2 sets of siblings who are half first cousins, 6 offspring have diagnoses of psychotic disorder. Homozygosity mapping revealed a 6.1-Mb homozygous region on chromosome 13q22.2-31.1 shared by all affected individuals, containing 13 protein-coding genes. Microsatellite analysis confirmed homozygosity for the affected haplotype in 12 further apparently unaffected members of the family. Psychiatric reports suggested an endophenotype of milder psychiatric illness in 4 of these individuals. Exome and genome sequencing revealed no potentially pathogenic coding or structural variants within the risk haplotype. Filtering for noncoding variants with a minor allele frequency of <0.05 identified 17 variants predicted to have significant effects, the 2 most significant being within or adjacent to the SCEL gene. RNA sequencing of blood from an affected homozygote showed the upregulation of transcription from NDFIP2 and SCEL. NDFIP2 is highly expressed in brain, unlike SCEL, and is involved in determining T helper (Th) cell type 1 and Th2 phenotypes, which have previously been implicated with schizophrenia.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:47 |
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| Enthalten in: |
Schizophrenia bulletin - 47(2021), 3 vom: 29. Apr., Seite 796-802 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mahmood, Tariq [VerfasserIn] |
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| Links: |
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| Themen: |
Case Reports |
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| Anmerkungen: |
Date Completed 22.11.2021 Date Revised 22.11.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/schbul/sbaa161 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM317269933 |
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| 245 | 1 | 2 | |a A Recessively Inherited Risk Locus on Chromosome 13q22-31 Conferring Susceptibility to Schizophrenia |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. | ||
| 520 | |a We report a consanguineous family in which schizophrenia segregates in a manner consistent with recessive inheritance of a rare, partial-penetrance susceptibility allele. From 4 marriages between 2 sets of siblings who are half first cousins, 6 offspring have diagnoses of psychotic disorder. Homozygosity mapping revealed a 6.1-Mb homozygous region on chromosome 13q22.2-31.1 shared by all affected individuals, containing 13 protein-coding genes. Microsatellite analysis confirmed homozygosity for the affected haplotype in 12 further apparently unaffected members of the family. Psychiatric reports suggested an endophenotype of milder psychiatric illness in 4 of these individuals. Exome and genome sequencing revealed no potentially pathogenic coding or structural variants within the risk haplotype. Filtering for noncoding variants with a minor allele frequency of <0.05 identified 17 variants predicted to have significant effects, the 2 most significant being within or adjacent to the SCEL gene. RNA sequencing of blood from an affected homozygote showed the upregulation of transcription from NDFIP2 and SCEL. NDFIP2 is highly expressed in brain, unlike SCEL, and is involved in determining T helper (Th) cell type 1 and Th2 phenotypes, which have previously been implicated with schizophrenia | ||
| 650 | 4 | |a Case Reports | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a consanguineous/endophenotype/homozygosity/ chromosome 13q/risk haplotype | |
| 700 | 1 | |a El-Asrag, Mohammed E |e verfasserin |4 aut | |
| 700 | 1 | |a Poulter, James A |e verfasserin |4 aut | |
| 700 | 1 | |a Cardno, Alastair G |e verfasserin |4 aut | |
| 700 | 1 | |a Tomlinson, Anneka |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmed, Sophia |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Amri, Ahmed |e verfasserin |4 aut | |
| 700 | 1 | |a Nazari, Jamshid |e verfasserin |4 aut | |
| 700 | 1 | |a Neill, Joanna |e verfasserin |4 aut | |
| 700 | 1 | |a Chamali, Rifka S |e verfasserin |4 aut | |
| 700 | 1 | |a Kiwan, Nancy |e verfasserin |4 aut | |
| 700 | 1 | |a Ghuloum, Suhaila |e verfasserin |4 aut | |
| 700 | 1 | |a Alhaj, Hamid A |e verfasserin |4 aut | |
| 700 | 1 | |a Randerson Moor, Juliette |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Shabana |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Amin, Hassen |e verfasserin |4 aut | |
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| 700 | 1 | |a Ali, Manir |e verfasserin |4 aut | |
| 700 | 1 | |a Clapcote, Steven J |e verfasserin |4 aut | |
| 700 | 1 | |a Inglehearn, Chris F |e verfasserin |4 aut | |
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