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Family with primary periodic paralysis and a mutation in MCM3AP , a gene implicated in mRNA transport
Author(s) -
Gustavsson Emil K.,
Follett Jordan,
Farrer Matthew J.,
Aasly Jan O.
Publication year - 2019
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.26622
Subject(s) - biology , mutation , genetics , gene , periodic paralysis , messenger rna , somatic cell , exome sequencing , paralysis , medicine , surgery
: Primary periodic paralyses (PPs) are rare genetic neuromuscular disorders commonly caused by mutations in genes related to ion channel function. However, 10%–20% of cases remain as genetically unexplained. Herein we present a family with PP with paralytic episodes generally lasting for 1–7 days at a time, associated with a drop in K + levels. Methods : Screening for mutations in known disease‐causing genes was negative, hence we performed whole‐exome sequencing of 5 family members. Results : Minichromosome maintenance 3–associated protein ( MCM3AP ) c.2615G>A (p.C872Y) was found to cosegregate with disease in the family and was not present in control subjects. The mutation is novel, highly conserved across multiple species, and predicted to be damaging. Discussion : MCM3AP encodes germinal center–associated nuclear protein (GANP), a protein involved in the export of certain messenger RNAs from the nucleus to the cytoplasm. Our findings suggest that a novel mutation in MCM3AP is associated with hypokalemic PP. Muscle Nerve , 2019