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Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder
PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata–Akhtar syndrome). METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome seq...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862064/ https://www.ncbi.nlm.nih.gov/pubmed/33173220 http://dx.doi.org/10.1038/s41436-020-00993-y |
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author | Brunet, Theresa McWalter, Kirsty Mayerhanser, Katharina Anbouba, Grace M. Armstrong-Javors, Amy Bader, Ingrid Baugh, Evan Begtrup, Amber Bupp, Caleb P. Callewaert, Bert L. Cereda, Anna Cousin, Margot A. Del Rey Jimenez, Juan C. Demmer, Laurie Dsouza, Nikita R. Fleischer, Nicole Gavrilova, Ralitza H. Ghate, Sumedha Graf, Elisabeth Green, Andrew Green, Sarah R. Iascone, Maria Kdissa, Ameni Klee, Dirk Klee, Eric W. Lancaster, Emily Lindstrom, Kristin Mayr, Johannes A. McEntagart, Meriel Meeks, Naomi J. L. Mittag, Dana Moore, Harrison Olsen, Anne K. Ortiz, Damara Parsons, Gretchen Pena, Loren D. M. Person, Richard E. Punj, Sumit Ramos-Rivera, Gonzalo Alonso Sacoto, Maria J. Guillen Bradley Schaefer, G. Schnur, Rhonda E. Scott, Tiana M. Scott, Daryl A. Serbinski, Carolyn R. Shashi, Vandana Siu, Victoria M. Stadheim, Barbro Fossøy Sullivan, Jennifer A. Švantnerová, Jana Velsher, Lea Wargowski, David S. Wentzensen, Ingrid M. Wieczorek, Dagmar Winkelmann, Juliane Yap, Patrick Zech, Michael Zimmermann, Michael T. Meitinger, Thomas Distelmaier, Felix Wagner, Matias |
author_facet | Brunet, Theresa McWalter, Kirsty Mayerhanser, Katharina Anbouba, Grace M. Armstrong-Javors, Amy Bader, Ingrid Baugh, Evan Begtrup, Amber Bupp, Caleb P. Callewaert, Bert L. Cereda, Anna Cousin, Margot A. Del Rey Jimenez, Juan C. Demmer, Laurie Dsouza, Nikita R. Fleischer, Nicole Gavrilova, Ralitza H. Ghate, Sumedha Graf, Elisabeth Green, Andrew Green, Sarah R. Iascone, Maria Kdissa, Ameni Klee, Dirk Klee, Eric W. Lancaster, Emily Lindstrom, Kristin Mayr, Johannes A. McEntagart, Meriel Meeks, Naomi J. L. Mittag, Dana Moore, Harrison Olsen, Anne K. Ortiz, Damara Parsons, Gretchen Pena, Loren D. M. Person, Richard E. Punj, Sumit Ramos-Rivera, Gonzalo Alonso Sacoto, Maria J. Guillen Bradley Schaefer, G. Schnur, Rhonda E. Scott, Tiana M. Scott, Daryl A. Serbinski, Carolyn R. Shashi, Vandana Siu, Victoria M. Stadheim, Barbro Fossøy Sullivan, Jennifer A. Švantnerová, Jana Velsher, Lea Wargowski, David S. Wentzensen, Ingrid M. Wieczorek, Dagmar Winkelmann, Juliane Yap, Patrick Zech, Michael Zimmermann, Michael T. Meitinger, Thomas Distelmaier, Felix Wagner, Matias |
author_sort | Brunet, Theresa |
collection | PubMed |
description | PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata–Akhtar syndrome). METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined. CONCLUSION: Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata–Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals. |
format | Online Article Text |
id | pubmed-7862064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-78620642021-02-24 Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder Brunet, Theresa McWalter, Kirsty Mayerhanser, Katharina Anbouba, Grace M. Armstrong-Javors, Amy Bader, Ingrid Baugh, Evan Begtrup, Amber Bupp, Caleb P. Callewaert, Bert L. Cereda, Anna Cousin, Margot A. Del Rey Jimenez, Juan C. Demmer, Laurie Dsouza, Nikita R. Fleischer, Nicole Gavrilova, Ralitza H. Ghate, Sumedha Graf, Elisabeth Green, Andrew Green, Sarah R. Iascone, Maria Kdissa, Ameni Klee, Dirk Klee, Eric W. Lancaster, Emily Lindstrom, Kristin Mayr, Johannes A. McEntagart, Meriel Meeks, Naomi J. L. Mittag, Dana Moore, Harrison Olsen, Anne K. Ortiz, Damara Parsons, Gretchen Pena, Loren D. M. Person, Richard E. Punj, Sumit Ramos-Rivera, Gonzalo Alonso Sacoto, Maria J. Guillen Bradley Schaefer, G. Schnur, Rhonda E. Scott, Tiana M. Scott, Daryl A. Serbinski, Carolyn R. Shashi, Vandana Siu, Victoria M. Stadheim, Barbro Fossøy Sullivan, Jennifer A. Švantnerová, Jana Velsher, Lea Wargowski, David S. Wentzensen, Ingrid M. Wieczorek, Dagmar Winkelmann, Juliane Yap, Patrick Zech, Michael Zimmermann, Michael T. Meitinger, Thomas Distelmaier, Felix Wagner, Matias Genet Med Article PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata–Akhtar syndrome). METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined. CONCLUSION: Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata–Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals. Nature Publishing Group US 2020-11-11 2021 /pmc/articles/PMC7862064/ /pubmed/33173220 http://dx.doi.org/10.1038/s41436-020-00993-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Brunet, Theresa McWalter, Kirsty Mayerhanser, Katharina Anbouba, Grace M. Armstrong-Javors, Amy Bader, Ingrid Baugh, Evan Begtrup, Amber Bupp, Caleb P. Callewaert, Bert L. Cereda, Anna Cousin, Margot A. Del Rey Jimenez, Juan C. Demmer, Laurie Dsouza, Nikita R. Fleischer, Nicole Gavrilova, Ralitza H. Ghate, Sumedha Graf, Elisabeth Green, Andrew Green, Sarah R. Iascone, Maria Kdissa, Ameni Klee, Dirk Klee, Eric W. Lancaster, Emily Lindstrom, Kristin Mayr, Johannes A. McEntagart, Meriel Meeks, Naomi J. L. Mittag, Dana Moore, Harrison Olsen, Anne K. Ortiz, Damara Parsons, Gretchen Pena, Loren D. M. Person, Richard E. Punj, Sumit Ramos-Rivera, Gonzalo Alonso Sacoto, Maria J. Guillen Bradley Schaefer, G. Schnur, Rhonda E. Scott, Tiana M. Scott, Daryl A. Serbinski, Carolyn R. Shashi, Vandana Siu, Victoria M. Stadheim, Barbro Fossøy Sullivan, Jennifer A. Švantnerová, Jana Velsher, Lea Wargowski, David S. Wentzensen, Ingrid M. Wieczorek, Dagmar Winkelmann, Juliane Yap, Patrick Zech, Michael Zimmermann, Michael T. Meitinger, Thomas Distelmaier, Felix Wagner, Matias Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder |
title | Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder |
title_full | Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder |
title_fullStr | Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder |
title_full_unstemmed | Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder |
title_short | Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder |
title_sort | defining the genotypic and phenotypic spectrum of x-linked msl3-related disorder |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862064/ https://www.ncbi.nlm.nih.gov/pubmed/33173220 http://dx.doi.org/10.1038/s41436-020-00993-y |
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