Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger-Huet anomaly

Abstract

BackgroundHereditary 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.AimsTo identify a causative gene for SOPH syndrome.MethodsGenomewide homozygosity mapping was conducted in 33 patients in 30 families.ResultsThe 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.ConclusionThese findings suggest that function of NBAS may associate with the pathogenesis of short stature syndrome as well as optic atrophy and Pelger-Huët anomaly.

Interaction between Common Genetic Variants and Total Fat Intake on Low-Density Lipoprotein Peak Particle Diameter: A Genome-Wide Association Study

“…Fourth, the protein encoded by NBAS is thought to be involved in Golgi-to-endoplasmic reticulum transport [38]. SNPs in the NBAS gene may be connected with the pathogenesis of the short stature syndrome, optic atrophy and Pelger-Huët anomaly, which is characterized by a neutrophil whose nucleus is hyposegmented [39]. Overall, the results are suggestive of the hypothesis that some SNPs in genes related to the immune system may alter the LDL particle size.…”

Autosomal recessive deafness 1A (DFNB1A) in Yakut population isolate in Eastern Siberia: extensive accumulation of the splice site mutation IVS1+1G>A in GJB2 gene as a result of founder effect

“…33 The Yakut population exhibits high rate of some Mendelian disorders, which are rare in other populations worldwide. High rates of spinocerebellar ataxia type 1 (SCA1), 32 myothonic dystrophy (DMPK), 26 oculopharyngeal muscular dystrophy (OPMD), 34 autosomal recessive methemoglobinemia (DIA1) 35 and two types of short stature disorders, 3-M (CUL7) and short stature with optic atrophy and Pelger-Huët anomaly (SOPH) syndrome (NBAS), 33,36 were previously found in Yakut population. We estimated the prevalence of DFNB1A associated with splice site IVS1+1G4A mutation in GJB2 gene as 16.2 in 100 000 in Yakut population, that is, higher compared with other common autosomal reccesive disorders found in Yakuts, such as autosomal recessive methemoglobinemia (14.9 in 100 000), 35 two types of short stature disorders, 3-M (10.0 in 100 000), 33 and SOPH syndromes (9.95 in 100 000).…”

“…We estimated the prevalence of DFNB1A associated with splice site IVS1+1G4A mutation in GJB2 gene as 16.2 in 100 000 in Yakut population, that is, higher compared with other common autosomal reccesive disorders found in Yakuts, such as autosomal recessive methemoglobinemia (14.9 in 100 000), 35 two types of short stature disorders, 3-M (10.0 in 100 000), 33 and SOPH syndromes (9.95 in 100 000). 36 Thus, we suggested that autosomal recessive deafness 1A (DFNB1A) associated with homozygous mutation IVS1+1G4A in GJB2 gene is the most common autosomal recessive disease among Yakuts.…”

“…31 Moreover, high frequency of some Mendelian disorders in the Yakut population was found to be a result of founder effect. [32][33][34][35][36] Preliminary mutational analysis of the coding region of GJB2 gene in deaf patients from the Sakha Republic revealed the presence of GJB2 mutations in 50.1% of Caucasian patients (Russians, Ukrainians, Ingush) and only in 7.2% of Asian patients (predominantly Yakuts). 37 We suggested that high prevalence of congenital HI in the Sakha Republic may be caused by mutations in non-coding region of GJB2 gene or in other genes responsible for hereditary forms of deafness among Yakuts.…”

Genome-wide association study of recalcitrant atopic dermatitis in Korean children

“…39 NBAS protein is expressed in epidermal skin cell, although it has not previously been implicated in chronic skin inflammatory diseases. 40 In contrast, genes at the 6q22.33, 10p14 and 15q24.3 locus are involved in immune dysregulation, which is a key pathogenic pathway in AD. The 6q22.33 and 10p14 loci include genes involved in adaptive immune responses, particularly in T cell differentiation.…”