PCSK5 mutation in a patient with the VACTERL association

Springer Science and Business Media LLC - Tập 8 - Trang 1-7 - 2015
Yukio Nakamura1, Shingo Kikugawa2, Shoji Seki3, Masahiko Takahata4, Norimasa Iwasaki4, Hidetomi Terai5, Mitsuhiro Matsubara6, Fumio Fujioka6, Hidehito Inagaki7, Tatsuya Kobayashi8, Tomoatsu Kimura3, Hiroki Kurahashi7, Hiroyuki Kato1
1Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
2DNA Chip Research Inc., Kanagawa, Japan
3Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama, Japan
4Department of Orthopaedic Surgery, Hokkaido University School of Medicine, Sapporo, Japan
5Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
6Department of Orthopaedic Surgery, Nagano Prefectural Children’s Hospital, Azumino, Japan
7Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan
8Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA

Tóm tắt

The VACTERL association is a typically sporadic, non-random collection of congenital anomalies that includes vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, renal anomalies, and limb abnormalities. Although several chromosomal aberrations and gene muta tions have been reported as disease-causative, these findings have been sparsely replicated to date. In the present study, whole exome sequencing of a case with the VACTERL association uncovered a novel frameshift mutation in the PCSK5 gene, which has been reported as one of the causative genes for the VACTERL association. Although this mutation appears potentially pathogenic in its functional aspects, it was also carried by the healthy father. Furthermore, a database survey revealed several other deleterious variants in the PCSK5 gene in the general population. Further studies are necessary to clarify the etiological role of the PCSK5 mutation in the VACTERL association.

Tài liệu tham khảo

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