dc.contributor.author | Parry, DA | |
dc.contributor.author | Martin, C-A | |
dc.contributor.author | Greene, P | |
dc.contributor.author | Marsh, JA | |
dc.contributor.author | Genomics England Research Consortium | |
dc.contributor.author | Blyth, M | |
dc.contributor.author | Cox, H | |
dc.contributor.author | Donnelly, D | |
dc.contributor.author | Greenhalgh, L | |
dc.contributor.author | Greville-Heygate, S | |
dc.contributor.author | Harrison, V | |
dc.contributor.author | Lachlan, K | |
dc.contributor.author | McKenna, C | |
dc.contributor.author | Quigley, AJ | |
dc.contributor.author | Rea, G | |
dc.contributor.author | Robertson, L | |
dc.contributor.author | Suri, M | |
dc.contributor.author | Jackson, AP | |
dc.date.accessioned | 2021-02-02T12:27:52Z | |
dc.date.available | 2020-09-17 | |
dc.date.available | 2021-02-02T12:27:52Z | |
dc.date.issued | 2020-10-09 | |
dc.identifier.citation | Parry, D.A., Martin, CA., Greene, P. et al. Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy. Genet Med (2020). https://doi.org/10.1038/s41436-020-00980-3 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/70067 | |
dc.description.abstract | PURPOSE: Lamins are the major component of nuclear lamina, maintaining structural integrity of the nucleus. Lamin A/C variants are well established to cause a spectrum of disorders ranging from myopathies to progeria, termed laminopathies. Phenotypes resulting from variants in LMNB1 and LMNB2 have been much less clearly defined. METHODS: We investigated exome and genome sequencing from the Deciphering Developmental Disorders Study and the 100,000 Genomes Project to identify novel microcephaly genes. RESULTS: Starting from a cohort of patients with extreme microcephaly, 13 individuals with heterozygous variants in the two human B-type lamins were identified. Recurrent variants were established to be de novo in nine cases and shown to affect highly conserved residues within the lamin ɑ-helical rod domain, likely disrupting interactions required for higher-order assembly of lamin filaments. CONCLUSION: We identify dominant pathogenic variants in LMNB1 and LMNB2 as a genetic cause of primary microcephaly, implicating a major structural component of the nuclear envelope in its etiology and defining a new form of laminopathy. The distinct nature of this lamin B-associated phenotype highlights the strikingly different developmental requirements for lamin paralogs and suggests a novel mechanism for primary microcephaly warranting future investigation. | en_US |
dc.language | eng | |
dc.relation.ispartof | Genet Med | |
dc.rights | Creative Commons Attribution 4.0 International License | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | LMNB1 | en_US |
dc.subject | LMNB2 | en_US |
dc.subject | laminopathy | en_US |
dc.subject | neurodevelopmental disorder | en_US |
dc.subject | primary microcephaly | en_US |
dc.title | Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy. | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1038/s41436-020-00980-3 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/33033404 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
dcterms.dateAccepted | 2020-09-17 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |