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Functional mRNA analysis reveals aberrant splicing caused by novel intronic mutation in WDR45 in NBIA patient
Author(s) -
Willoughby Josh,
DuffFarrier Celia,
Desurkar Archana,
Kurian Manju,
Raghavan Ashok,
Balasubramanian Meena
Publication year - 2018
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38656
Subject(s) - rna splicing , neurodegeneration , exome sequencing , biology , mutation , phenotype , genetics , in silico , global developmental delay , gene , alternative splicing , exome , disease , medicine , messenger rna , pathology , rna
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.