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Am J Med Genet A. 2018 May;176(5):1049-1054. doi: 10.1002/ajmg.a.38656.

Functional mRNA analysis reveals aberrant splicing caused by novel intronic mutation in WDR45 in NBIA patient.

Author information

1
Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.
2
Bristol Genetics Laboratory, Pathology Sciences, Southmead Hospital, Bristol, United Kingdom.
3
Department of Neurology, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.
4
Department of Paediatric Neurology, Great Ormond Street Hospital, London, United Kingdom.
5
Department of Radiology, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.
6
Wellcome Sanger Institute, Cambridge, UK.
7
Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.

Abstract

WDR45 gene-associated neurodegeneration with brain iron accumulation (NBIA), referred to as beta-propeller protein-associated neurodegeneration (BPAN), is a rare disorder that presents with a very nonspecific clinical phenotype in children constituting global developmental delay. This case report illustrates the power of a combination of trio exome sequencing, in silico splicing analysis, and mRNA analysis to provide sufficient evidence for pathogenicity of a relatively intronic variant in WDR45, and in so doing, find a genetic diagnosis for a 6-year-old patient with developmental delay and seizures, a diagnosis which may otherwise have only been found once the characteristic MRI patterns of the disease became more obvious in young adulthood.

KEYWORDS:

MRI-brain; WDR45; cultured fibroblasts; in silico analysis; intronic; iron accumulation; mRNA analysis; mutation; splicing

PMID:
29681108
DOI:
10.1002/ajmg.a.38656
[Indexed for MEDLINE]

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