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Hum Genet. 2018 Dec;137(11-12):905-909. doi: 10.1007/s00439-018-1950-8. Epub 2018 Oct 27.

Lowry-Wood syndrome: further evidence of association with RNU4ATAC, and correlation between genotype and phenotype.

Author information

1
Divisions of Medical Genetics, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada.
2
CHU Sainte-Justine Research Center, Montreal, QC, Canada.
3
Neonatology and Neonatal Intensive Care Unit, Maternal and Child Department, University of Parma, Parma, Italy.
4
Clinical Genetics Department, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
5
Laboratory of Human Genetics, Galliera Hospital, Genoa, Italy.
6
Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
7
Department of Translational Medicine, Federico II University of Naples, Naples, Italy.
8
Divisions of Medical Genetics, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada. p.campeau@umontreal.ca.

Abstract

Lowry-Wood syndrome (LWS) is a skeletal dysplasia characterized by multiple epiphyseal dysplasia associated with microcephaly, developmental delay and intellectual disability, and eye involvement. Pathogenic variants in RNU4ATAC, an RNA of the minor spliceosome important for the excision of U12-dependent introns, have been recently associated with LWS. This gene had previously also been associated with microcephalic osteodysplastic primordial dwarfism (MOPD) and Roifman syndrome (RS), two distinct conditions which share with LWS some skeletal and neurological anomalies. We performed exome sequencing in two individuals with Lowry-Wood syndrome. We report RNU4ATAC pathogenic variants in two further patients. Moreover, an analysis of all RNU4ATAC variants reported so far showed that FitCons scores for nucleotides mutated in the more severe MOPD are higher than RS or LWS and that they were more frequently located in the 5' Stem-Loop of the RNA critical for the formation of the U4/U6.U5 tri-snRNP complex, whereas the variants are more dispersed in the other conditions. We are thus confirming that RNU4ATAC is the gene responsible for LWS and provide a genotype-phenotype correlation analysis.

PMID:
30368667
DOI:
10.1007/s00439-018-1950-8
[Indexed for MEDLINE]

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