Low, KJ;
Ansari, M;
Abou Jamra, R;
Clarke, A;
El Chehadeh, S;
FitzPatrick, DR;
Greenslade, M;
Henderson, A;
Hurst, J;
Keller, K;
et al.
Low, KJ; Ansari, M; Abou Jamra, R; Clarke, A; El Chehadeh, S; FitzPatrick, DR; Greenslade, M; Henderson, A; Hurst, J; Keller, K; Kuentz, P; Prescott, T; Roessler, F; Selmer, KK; Schneider, MC; Stewart, F; Tatton-Brown, K; Thevenon, J; Vigeland, MD; Vogt, J; Willems, M; Zonana, J; Study, DDD; Smithson, SF
(2017)
PUF60 variants cause a syndrome of ID, short stature, microcephaly, coloboma, craniofacial, cardiac, renal and spinal features.
Eur J Hum Genet, 25 (5).
pp. 552-559.
ISSN 1476-5438
https://doi.org/10.1038/ejhg.2017.27
SGUL Authors: Tatton-Brown, Katrina Louise
Abstract
PUF60 encodes a nucleic acid-binding protein, a component of multimeric complexes regulating RNA splicing and transcription. In 2013, patients with microdeletions of chromosome 8q24.3 including PUF60 were found to have developmental delay, microcephaly, craniofacial, renal and cardiac defects. Very similar phenotypes have been described in six patients with variants in PUF60, suggesting that it underlies the syndrome. We report 12 additional patients with PUF60 variants who were ascertained using exome sequencing: six through the Deciphering Developmental Disorders Study and six through similar projects. Detailed phenotypic analysis of all patients was undertaken. All 12 patients had de novo heterozygous PUF60 variants on exome analysis, each confirmed by Sanger sequencing: four frameshift variants resulting in premature stop codons, three missense variants that clustered within the RNA recognition motif of PUF60 and five essential splice-site (ESS) variant. Analysis of cDNA from a fibroblast cell line derived from one of the patients with an ESS variants revealed aberrant splicing. The consistent feature was developmental delay and most patients had short stature. The phenotypic variability was striking; however, we observed similarities including spinal segmentation anomalies, congenital heart disease, ocular colobomata, hand anomalies and (in two patients) unilateral renal agenesis/horseshoe kidney. Characteristic facial features included micrognathia, a thin upper lip and long philtrum, narrow almond-shaped palpebral fissures, synophrys, flared eyebrows and facial hypertrichosis. Heterozygote loss-of-function variants in PUF60 cause a phenotype comprising growth/developmental delay and craniofacial, cardiac, renal, ocular and spinal anomalies, adding to disorders of human development resulting from aberrant RNA processing/spliceosomal function.
Item Type: |
Article
|
Additional Information: |
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s
Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
© The Author(s) 2017 |
Keywords: |
Abnormalities, Multiple, Cells, Cultured, Child, Codon, Terminator, Exome, Female, Heterozygote, Humans, Intellectual Disability, Male, Microcephaly, Mutation, Missense, Phenotype, RNA Splicing Factors, Repressor Proteins, Syndrome, Genetics & Heredity, 0604 Genetics |
SGUL Research Institute / Research Centre: |
Academic Structure > Institute of Medical & Biomedical Education (IMBE) |
Journal or Publication Title: |
Eur J Hum Genet |
ISSN: |
1476-5438 |
Language: |
eng |
Dates: |
Date | Event |
---|
22 March 2017 | Published | 31 January 2017 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
|
PubMed ID: |
28327570 |
Web of Science ID: |
WOS:000399406200007 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/109922 |
Publisher's version: |
https://doi.org/10.1038/ejhg.2017.27 |
Statistics
Item downloaded times since 27 Jun 2018.
Actions (login required)
![Edit Item](/style/images/action_view.png) |
Edit Item |