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Deletion 16p13.11 uncovers NDE1 mutations on the non-deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption

Deletions of 16p13.11 have been associated with a variety of phenotypes, and have also been found in normal individuals. We report on two unrelated patients with severe microcephaly, agenesis of the corpus callosum, scalp rugae, and a fetal brain disruption (FBD)-like phenotype with inherited deleti...

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Autores principales: Paciorkowski, Alex R, Keppler-Noreuil, Kim, Robinson, Luther, Sullivan, Christopher, Sajan, Samin, Christian, Susan L, Bukshpun, Polina, Gabriel, Stacy B, Gleeson, Joseph G, Sherr, Elliott H, Dobyns, William B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689850/
https://www.ncbi.nlm.nih.gov/pubmed/23704059
http://dx.doi.org/10.1002/ajmg.a.35969
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author Paciorkowski, Alex R
Keppler-Noreuil, Kim
Robinson, Luther
Sullivan, Christopher
Sajan, Samin
Christian, Susan L
Bukshpun, Polina
Gabriel, Stacy B
Gleeson, Joseph G
Sherr, Elliott H
Dobyns, William B
author_facet Paciorkowski, Alex R
Keppler-Noreuil, Kim
Robinson, Luther
Sullivan, Christopher
Sajan, Samin
Christian, Susan L
Bukshpun, Polina
Gabriel, Stacy B
Gleeson, Joseph G
Sherr, Elliott H
Dobyns, William B
author_sort Paciorkowski, Alex R
collection PubMed
description Deletions of 16p13.11 have been associated with a variety of phenotypes, and have also been found in normal individuals. We report on two unrelated patients with severe microcephaly, agenesis of the corpus callosum, scalp rugae, and a fetal brain disruption (FBD)-like phenotype with inherited deletions of 16p13.11. The first patient was subsequently found on whole exome sequencing to have a nonsense mutation (p.R44X) in NDE1 on the non-deleted chromosome 16 homolog. We then undertook copy number studies of 16p13.11 and sequencing of NDE1 in nine additional patients with a similar severe microcephaly, agenesis of the corpus callosum, and FBD-like phenotype. The second patient was found to have an inherited deletion of the entire NDE1 gene combined with a frameshift mutation (c.1020-1021het_delGA) in the non-deleted NDE1. These observations broaden the phenotype seen in NDE1-related microcephaly to include FBD. These data also represent the second described syndrome, after Bernard-Soulier syndrome, where an autosomal recessive condition combines an inherited segmental duplication mediated deletion with a mutation in a gene within the non-deleted homolog. Finally, we performed informatics analysis of the 16p13.11 gene content, and found that there are many genes within the region with evidence for role(s) in brain development. Sequencing of other candidate genes in this region in patients with deletion 16p13.11 and more severe neurophenotypes may be warranted.
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spelling pubmed-36898502013-11-03 Deletion 16p13.11 uncovers NDE1 mutations on the non-deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption Paciorkowski, Alex R Keppler-Noreuil, Kim Robinson, Luther Sullivan, Christopher Sajan, Samin Christian, Susan L Bukshpun, Polina Gabriel, Stacy B Gleeson, Joseph G Sherr, Elliott H Dobyns, William B Am J Med Genet A Research Articles Deletions of 16p13.11 have been associated with a variety of phenotypes, and have also been found in normal individuals. We report on two unrelated patients with severe microcephaly, agenesis of the corpus callosum, scalp rugae, and a fetal brain disruption (FBD)-like phenotype with inherited deletions of 16p13.11. The first patient was subsequently found on whole exome sequencing to have a nonsense mutation (p.R44X) in NDE1 on the non-deleted chromosome 16 homolog. We then undertook copy number studies of 16p13.11 and sequencing of NDE1 in nine additional patients with a similar severe microcephaly, agenesis of the corpus callosum, and FBD-like phenotype. The second patient was found to have an inherited deletion of the entire NDE1 gene combined with a frameshift mutation (c.1020-1021het_delGA) in the non-deleted NDE1. These observations broaden the phenotype seen in NDE1-related microcephaly to include FBD. These data also represent the second described syndrome, after Bernard-Soulier syndrome, where an autosomal recessive condition combines an inherited segmental duplication mediated deletion with a mutation in a gene within the non-deleted homolog. Finally, we performed informatics analysis of the 16p13.11 gene content, and found that there are many genes within the region with evidence for role(s) in brain development. Sequencing of other candidate genes in this region in patients with deletion 16p13.11 and more severe neurophenotypes may be warranted. Blackwell Publishing Ltd 2013-07 2013-05-23 /pmc/articles/PMC3689850/ /pubmed/23704059 http://dx.doi.org/10.1002/ajmg.a.35969 Text en Copyright © 2013 Wiley Periodicals, Inc. http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Research Articles
Paciorkowski, Alex R
Keppler-Noreuil, Kim
Robinson, Luther
Sullivan, Christopher
Sajan, Samin
Christian, Susan L
Bukshpun, Polina
Gabriel, Stacy B
Gleeson, Joseph G
Sherr, Elliott H
Dobyns, William B
Deletion 16p13.11 uncovers NDE1 mutations on the non-deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption
title Deletion 16p13.11 uncovers NDE1 mutations on the non-deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption
title_full Deletion 16p13.11 uncovers NDE1 mutations on the non-deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption
title_fullStr Deletion 16p13.11 uncovers NDE1 mutations on the non-deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption
title_full_unstemmed Deletion 16p13.11 uncovers NDE1 mutations on the non-deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption
title_short Deletion 16p13.11 uncovers NDE1 mutations on the non-deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption
title_sort deletion 16p13.11 uncovers nde1 mutations on the non-deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689850/
https://www.ncbi.nlm.nih.gov/pubmed/23704059
http://dx.doi.org/10.1002/ajmg.a.35969
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