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Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome
Strømme syndrome is an ultra-rare primary ciliopathy with clinical variability. The syndrome is caused by bi-allelic variants in CENPF, a protein with key roles in both chromosomal segregation and ciliogenesis. We report three unrelated patients with Strømme syndrome and, using high-throughput seque...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671177/ https://www.ncbi.nlm.nih.gov/pubmed/38002928 http://dx.doi.org/10.3390/genes14111985 |
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author | Misceo, Doriana Senaratne, Lokuliyanage Dona Samudita Mero, Inger-Lise Sundaram, Arvind Y. M. Bjørnstad, Pål Marius Szczałuba, Krzysztof Gasperowicz, Piotr Kamien, Benjamin Nedregaard, Bård Holmgren, Asbjørn Strømme, Petter Frengen, Eirik |
author_facet | Misceo, Doriana Senaratne, Lokuliyanage Dona Samudita Mero, Inger-Lise Sundaram, Arvind Y. M. Bjørnstad, Pål Marius Szczałuba, Krzysztof Gasperowicz, Piotr Kamien, Benjamin Nedregaard, Bård Holmgren, Asbjørn Strømme, Petter Frengen, Eirik |
author_sort | Misceo, Doriana |
collection | PubMed |
description | Strømme syndrome is an ultra-rare primary ciliopathy with clinical variability. The syndrome is caused by bi-allelic variants in CENPF, a protein with key roles in both chromosomal segregation and ciliogenesis. We report three unrelated patients with Strømme syndrome and, using high-throughput sequencing approaches, we identified novel pathogenic variants in CENPF, including one structural variant, giving a genetic diagnosis to the patients. Patient 1 was a premature baby who died at 26 days with congenital malformations affecting many organs including the brain, eyes, and intestine. She was homozygous for a donor splice variant in CENPF, NM_016343.3:c.1068+1G>A, causing skipping of exon 7, resulting in a frameshift. Patient 2 was a female with intestinal atresia, microcephaly, and a Peters anomaly. She had normal developmental milestones at the age of 7 years. She is compound heterozygous for CENPF NM_016343.3:c.5920dup and c.8991del, both frameshift. Patient 3 was a male with anomalies of the brain, eye, intestine, and kidneys. He was compound heterozygous for CENPF p.(Glu298Ter), and a 5323 bp deletion covering exon 1. CENPF exon 1 is flanked by repetitive sequences that may represent a site of a recurrent structural variation, which should be a focus in patients with Strømme syndrome of unknown etiology. |
format | Online Article Text |
id | pubmed-10671177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106711772023-10-24 Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome Misceo, Doriana Senaratne, Lokuliyanage Dona Samudita Mero, Inger-Lise Sundaram, Arvind Y. M. Bjørnstad, Pål Marius Szczałuba, Krzysztof Gasperowicz, Piotr Kamien, Benjamin Nedregaard, Bård Holmgren, Asbjørn Strømme, Petter Frengen, Eirik Genes (Basel) Article Strømme syndrome is an ultra-rare primary ciliopathy with clinical variability. The syndrome is caused by bi-allelic variants in CENPF, a protein with key roles in both chromosomal segregation and ciliogenesis. We report three unrelated patients with Strømme syndrome and, using high-throughput sequencing approaches, we identified novel pathogenic variants in CENPF, including one structural variant, giving a genetic diagnosis to the patients. Patient 1 was a premature baby who died at 26 days with congenital malformations affecting many organs including the brain, eyes, and intestine. She was homozygous for a donor splice variant in CENPF, NM_016343.3:c.1068+1G>A, causing skipping of exon 7, resulting in a frameshift. Patient 2 was a female with intestinal atresia, microcephaly, and a Peters anomaly. She had normal developmental milestones at the age of 7 years. She is compound heterozygous for CENPF NM_016343.3:c.5920dup and c.8991del, both frameshift. Patient 3 was a male with anomalies of the brain, eye, intestine, and kidneys. He was compound heterozygous for CENPF p.(Glu298Ter), and a 5323 bp deletion covering exon 1. CENPF exon 1 is flanked by repetitive sequences that may represent a site of a recurrent structural variation, which should be a focus in patients with Strømme syndrome of unknown etiology. MDPI 2023-10-24 /pmc/articles/PMC10671177/ /pubmed/38002928 http://dx.doi.org/10.3390/genes14111985 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Misceo, Doriana Senaratne, Lokuliyanage Dona Samudita Mero, Inger-Lise Sundaram, Arvind Y. M. Bjørnstad, Pål Marius Szczałuba, Krzysztof Gasperowicz, Piotr Kamien, Benjamin Nedregaard, Bård Holmgren, Asbjørn Strømme, Petter Frengen, Eirik Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome |
title | Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome |
title_full | Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome |
title_fullStr | Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome |
title_full_unstemmed | Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome |
title_short | Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome |
title_sort | novel loss of function variants in cenpf including a large intragenic deletion in patients with strømme syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671177/ https://www.ncbi.nlm.nih.gov/pubmed/38002928 http://dx.doi.org/10.3390/genes14111985 |
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