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Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger–Huët anomaly
  1. Nadezda Maksimova1,
  2. Kenju Hara2,
  3. Irina Nikolaeva1,
  4. Tan Chun-Feng3,
  5. Tomoaki Usui4,
  6. Mineo Takagi4,
  7. Yasushi Nishihira3,
  8. Akinori Miyashita5,
  9. Hiroshi Fujiwara6,
  10. Tokuhide Oyama4,
  11. Anna Nogovicina7,
  12. Aitalina Sukhomyasova7,
  13. Svetlana Potapova7,
  14. Ryozo Kuwano5,
  15. Hitoshi Takahashi3,
  16. Masatoyo Nishizawa2,
  17. Osamu Onodera8
  1. 1Department of Molecular Genetics, Yakut Scientific Center of Complex Medical Problems, Siberian Department of Russian Academy of Medical Science, Yakutsk, Russia
  2. 2Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
  3. 3Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
  4. 4Division of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, University of Niigata, Niigata, Japan
  5. 5Department of Molecular Genetics, Center for Bioresource-based Researches, Brain Research Institute, Niigata University, Japan
  6. 6Division of Dermatology, Graduate School of Medical and Dental Sciences, University of Niigata, Niigata, Japan
  7. 7Republican Hospital No. 1 - National Medical Centre, Yakutsk, Russia
  8. 8Department of Molecular Neuroscience, Center for Bioresource-based Researches, Brain Research Institute, Niigata University, Japan
  1. Correspondence to Dr Osamu Onodera, Department of Molecular Neuroscience, Resource Branch for Brain Disease, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata 951-8520, Japan; onodera{at}


Background Hereditary short stature syndromes are clinically and genetically heterogeneous disorders and the cause have not been fully identified. Yakuts are a population isolated in Asia; they live in the far east of the Russian Federation and have a high prevalence of hereditary short stature syndrome including 3-M syndrome. A novel short stature syndrome in Yakuts is reported here, which is characterised by autosomal recessive inheritance, severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, Pelger-Huët anomaly of leucocytes, and optic atrophy with loss of visual acuity and colour vision. This new syndrome is designated as short stature with optic atrophy and Pelger-Huët anomaly (SOPH) syndrome.

Aims To identify a causative gene for SOPH syndrome.

Methods Genomewide homozygosity mapping was conducted in 33 patients in 30 families.

Results The disease locus was mapped to the 1.1 Mb region on chromosome 2p24.3, including the neuroblastoma amplified sequence (NBAS) gene. Subsequently, 33 of 34 patients were identified with SOPH syndrome and had a 5741G/A nucleotide substitution (resulting in the amino acid substitution R1914H) in the NBAS gene in the homozygous state. None of the 203 normal Yakuts individuals had this substitution in the homozygous state. Immunohistochemical analysis revealed that the NBAS protein is well expressed in retinal ganglion cells, epidermal skin cells, and leucocyte cytoplasm in controls as well as a patient with SOPH syndrome.

Conclusion These findings suggest that function of NBAS may associate with the pathogenesis of short stature syndrome as well as optic atrophy and Pelger-Huët anomaly.

  • Short stature
  • Yakuts
  • Pelger-Huët anomaly
  • optic atrophy
  • NBAS
  • diagnosis
  • endocrinology
  • clinical genetics
  • haematology (incl blood transfusion)
  • ophthalmology

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  • NM and KH contributed equally to this work.

  • Funding This study was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas ‘Advanced Brain Science Project’ and ‘Applied Genomics’, a grant for Young Researchers within the framework of the Program of the Japan-Russian Youth Exchange and HUGO Grant travel awards, and a Grant for the Promotion of Niigata University Research Projects.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the institutional review board of Niigata University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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