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Novel compound heterozygous DPH1 mutations in a patient with the unique clinical features of airway obstruction and external genital abnormalities

Authors
  • Nakajima, Junya1
  • Oana, Shingo1
  • Sakaguchi, Tomohiro2
  • Nakashima, Mitsuko2
  • Numabe, Hironao1
  • Kawashima, Hisashi1
  • Matsumoto, Naomichi2
  • Miyake, Noriko2
  • 1 Tokyo Medical University, Department of Pediatrics, Tokyo, Japan , Tokyo (Japan)
  • 2 Yokohama City University Graduate School of Medicine, Department of Human Genetics, Yokohama, Japan , Yokohama (Japan)
Type
Published Article
Journal
Journal of Human Genetics
Publisher
Springer Nature
Publication Date
Jan 23, 2018
Volume
63
Issue
4
Pages
529–532
Identifiers
DOI: 10.1038/s10038-017-0399-2
Source
Springer Nature
License
Yellow

Abstract

The diphthamide biosynthesis 1 (DPH1) gene encodes one of the essential components of the enzyme catalyzing the first step of diphthamide formation on eukaryotic elongation factor 2 (EEF2). Diphthamide is the posttranslationally modified histidine residue on EEF2 that promotes protein chain elongation in the ribosome. DPH1 defects result in a failure of protein synthesis involving EEF2, leading to growth defects, embryonic lethality, and cell death. In humans, DPH1 mutations cause developmental delay with a short stature, dysmorphic features, and sparse hair, and are inherited in an autosomal recessive manner (MIM#616901). To date, only two homozygous missense mutations in DPH1 (c.17T>A, p.Met6Lys and c.701T>C, p.Leu234Pro) have been reported. We used WES to identify novel compound heterozygous mutations in DPH1 (c.289delG, p.Glu97Lysfs*8 and c.491T>C, p.Leu164Pro) in a patient from a nonconsanguineous family presenting with intellectual disability, a short stature, craniofacial abnormalities, and external genital abnormalities. The clinical phenotype of all patients with DPH1 mutations, including the current patient, revealed core features, although the external genital anomaly was newly recognized in our case.

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