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A unique TBX5 microdeletion with microinsertion detected in patient with Holt–Oram syndrome
Author(s) -
Morine Mikio,
Kohmoto Tomohiro,
Masuda Kiyoshi,
Inagaki Hidehito,
Watanabe Miki,
Naruto Takuya,
Kurahashi Hiroki,
Maeda Kazuhisa,
Imoto Issei
Publication year - 2015
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.37359
Subject(s) - genetics , mutation , germline , biology , microbiology and biotechnology , gene
Holt–Oram syndrome (HOS) is an autosomal dominant condition characterized by upper limb and congenital heart defects and caused by numerous germline mutations of TBX5 producing preterminal stop codons. Here, we report on a novel and unusual heterozygous TBX5 microdeletion with microinsertion (microindel) mutation (c.627delinsGTGACTCAGGAAACGCTTTCCTGA), which is predicted to synthesize a truncated TBX5 protein, detected in a sporadic patient with clinical features of HOS prenatally diagnosed by ultrasonography. This uncommon and relatively large inserted sequence contains sequences derived from nearby but not adjacent templates on both sense and antisense strands, suggesting two possible models, which require no repeat sequences, causing this complex microindel through the bypass of large DNA adducts via an error‐prone DNA polymerase‐mediated translesion synthesis. © 2015 Wiley Periodicals, Inc.