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Novel compound heterozygous EPG5 mutations consisted with a missense mutation and a microduplication in the exon 1 region identified in a Japanese patient with Vici syndrome
Author(s) -
Shimada Shino,
Hirasawa Kyoko,
Takeshita Akiko,
Nakatsukasa Hidetsugu,
YamamotoShimojima Keiko,
Imaizumi Taichi,
Nagata Satoru,
Yamamoto Toshiyuki
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.40500
Subject(s) - missense mutation , exon , genetics , mutation , compound heterozygosity , biology , medicine , gene
Vici syndrome is a rare, autosomal recessive, multisystem disorder, characterized by agenesis of the corpus callosum, cataracts, psychomotor delay, cardiomyopathy, hypopigmentation, and recurrent infections. Mutations in the ectopic P‐granules autophagy protein 5 homolog gene ( EPG5 ), which encodes a key autophagy regulator, are responsible for this syndrome. A 3‐year‐old Japanese girl manifesting similar symptoms to those found in patients with Vici syndrome showed intractable diarrhea, rather than immunodeficiency. Whole exome sequencing identified only a heterozygous variant in EPG5 , NM_020964.2(EPG5):c.3389A > C (p.His1130Pro), which was inherited from her mother. Sequencing analyses of the EPG5 messenger RNA showed only an altered nucleotide “C” at position, c.3389, indicating decreased expression of the wild‐type allele. Microarray‐based comparative genomic hybridization revealed a de novo microduplication in the exon 1 region. Large exon deletions and duplications of EPG5 have never been reported so far. This was considered the cause of the decreased expression of the wild‐type allele. In conclusion, we successfully identified novel compound heterozygous mutations in EPG5 in a patient who was clinically considered to have Vici syndrome.