title: Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger-Huët anomaly.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Genetics, Yakut Scientific Center of Complex Medical Problems, Siberian Department of Russian Academy of Medical Science, Yakutsk, Russia.
authors.forename: Nadezda
authors.initials: N
authors.lastname: Maksimova
authors.forename: Kenju
authors.initials: K
authors.lastname: Hara
authors.forename: Irina
authors.initials: I
authors.lastname: Nikolaeva
authors.forename: Tan
authors.initials: T
authors.lastname: Chun-Feng
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Usui
authors.forename: Mineo
authors.initials: M
authors.lastname: Takagi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nishihira
authors.forename: Akinori
authors.initials: A
authors.lastname: Miyashita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Tokuhide
authors.initials: T
authors.lastname: Oyama
authors.forename: Anna
authors.initials: A
authors.lastname: Nogovicina
authors.forename: Aitalina
authors.initials: A
authors.lastname: Sukhomyasova
authors.forename: Svetlana
authors.initials: S
authors.lastname: Potapova
authors.forename: Ryozo
authors.initials: R
authors.lastname: Kuwano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D001827:Body Height / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D004392:Dwarfism / Q000150:complications* / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D009896:Optic Atrophy / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D010381:Pelger-Huet Anomaly / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D011859:Radiography; D013577:Syndrome; D055815:Young Adult
chemical_list: C117339:NBAS protein, human; D009363:Neoplasm Proteins