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Homozygous noncanonical splice variant in LSM1 in two siblings with multiple congenital anomalies and global developmental delay
Two siblings, one male and one female, ages 6 and 13 yr old, have similar clinical features of global developmental delay, multiple congenital anomalies affecting the cardiac, genitourinary, and skeletal systems, and abnormal eye movements. Whole-genome sequencing revealed a homozygous splice varian...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549555/ https://www.ncbi.nlm.nih.gov/pubmed/31010896 http://dx.doi.org/10.1101/mcs.a004101 |
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author | Okur, Volkan LeDuc, Charles A. Guzman, Edwin Valivullah, Zaheer M. Anyane-Yeboa, Kwame Chung, Wendy K. |
author_facet | Okur, Volkan LeDuc, Charles A. Guzman, Edwin Valivullah, Zaheer M. Anyane-Yeboa, Kwame Chung, Wendy K. |
author_sort | Okur, Volkan |
collection | PubMed |
description | Two siblings, one male and one female, ages 6 and 13 yr old, have similar clinical features of global developmental delay, multiple congenital anomalies affecting the cardiac, genitourinary, and skeletal systems, and abnormal eye movements. Whole-genome sequencing revealed a homozygous splice variant (NM_014462.3:c.231+4A>C) in LSM1 that segregated with the phenotype in the family. LSM1 has a role in pre-mRNA splicing and degradation. Expression studies revealed absence of expression of the canonical isoform in the affected individuals. The Lsm1 knockout mice have a partially overlapping phenotype that affects the brain, heart, and eye. To our knowledge, LSM1 has not been associated with any human disorder; however, the tissue expression pattern, gene constraint, and the similarity of the phenotype in our patients and the knockout mice models suggest it has a role in the development of multiple organ systems in humans. |
format | Online Article Text |
id | pubmed-6549555 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-65495552019-06-19 Homozygous noncanonical splice variant in LSM1 in two siblings with multiple congenital anomalies and global developmental delay Okur, Volkan LeDuc, Charles A. Guzman, Edwin Valivullah, Zaheer M. Anyane-Yeboa, Kwame Chung, Wendy K. Cold Spring Harb Mol Case Stud Research Report Two siblings, one male and one female, ages 6 and 13 yr old, have similar clinical features of global developmental delay, multiple congenital anomalies affecting the cardiac, genitourinary, and skeletal systems, and abnormal eye movements. Whole-genome sequencing revealed a homozygous splice variant (NM_014462.3:c.231+4A>C) in LSM1 that segregated with the phenotype in the family. LSM1 has a role in pre-mRNA splicing and degradation. Expression studies revealed absence of expression of the canonical isoform in the affected individuals. The Lsm1 knockout mice have a partially overlapping phenotype that affects the brain, heart, and eye. To our knowledge, LSM1 has not been associated with any human disorder; however, the tissue expression pattern, gene constraint, and the similarity of the phenotype in our patients and the knockout mice models suggest it has a role in the development of multiple organ systems in humans. Cold Spring Harbor Laboratory Press 2019-06 /pmc/articles/PMC6549555/ /pubmed/31010896 http://dx.doi.org/10.1101/mcs.a004101 Text en © 2019 Okur et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted reuse and redistribution provided that the original author and source are credited. |
spellingShingle | Research Report Okur, Volkan LeDuc, Charles A. Guzman, Edwin Valivullah, Zaheer M. Anyane-Yeboa, Kwame Chung, Wendy K. Homozygous noncanonical splice variant in LSM1 in two siblings with multiple congenital anomalies and global developmental delay |
title | Homozygous noncanonical splice variant in LSM1 in two siblings with multiple congenital anomalies and global developmental delay |
title_full | Homozygous noncanonical splice variant in LSM1 in two siblings with multiple congenital anomalies and global developmental delay |
title_fullStr | Homozygous noncanonical splice variant in LSM1 in two siblings with multiple congenital anomalies and global developmental delay |
title_full_unstemmed | Homozygous noncanonical splice variant in LSM1 in two siblings with multiple congenital anomalies and global developmental delay |
title_short | Homozygous noncanonical splice variant in LSM1 in two siblings with multiple congenital anomalies and global developmental delay |
title_sort | homozygous noncanonical splice variant in lsm1 in two siblings with multiple congenital anomalies and global developmental delay |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549555/ https://www.ncbi.nlm.nih.gov/pubmed/31010896 http://dx.doi.org/10.1101/mcs.a004101 |
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