RT Journal Article
SR Electronic
T1 Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger–Huët anomaly
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 538
OP 548
DO 10.1136/jmg.2009.074815
VO 47
IS 8
A1 Nadezda Maksimova
A1 Kenju Hara
A1 Irina Nikolaeva
A1 Tan Chun-Feng
A1 Tomoaki Usui
A1 Mineo Takagi
A1 Yasushi Nishihira
A1 Akinori Miyashita
A1 Hiroshi Fujiwara
A1 Tokuhide Oyama
A1 Anna Nogovicina
A1 Aitalina Sukhomyasova
A1 Svetlana Potapova
A1 Ryozo Kuwano
A1 Hitoshi Takahashi
A1 Masatoyo Nishizawa
A1 Osamu Onodera
YR 2010
UL http://jmg.bmj.com/content/47/8/538.abstract
AB 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.