Determination of the mechanism causing mesomelic dysplasia, Kantaputra type

Abstract

Mesomelic dysplasia, kantaputra type (MDK) is a new type of autosomal dominant skeletal dysplasia. All of patients were characterized by disproportionate dwarfism, bilateral shortening of the forearms/lower-legs, carpal/tarsal synostosis, and dorsolateral foot deviation. To date, only two families of MDK were reported., first in Thai and second in Dutch family. A linkage analysis mapped the MDK to 2q24-q32. However, there was no further study to this disease. Previous studies have shown that mutation in coding region of some genes in 2q31 region, for instance; HOXD13, HOXD10, caused abnormalities in limb development. Moreover, mutation in regulatory region can also caused phenotype similar to MDK as seen in Ulnaless mice and mesomelic dysplasia patients which implied the existence of regulatory region called Global control region (GCR). Based on evidences from human and mouse model, we screened the mutation in coding region of HOXD10, HOXD11, EVX-2 and LNP gene, located within 2q31 region, in MDK patients. We also determined a level of LNP gene expression by using relative quantification method in a MDK patient compared to normal controls to find the clue for mutation in the regulatory region. Our result showed no mutation in the coding regions of candidate genes. However, we found upregulation of LNP gene expression in the MDK patient which showed three times higher than normal controls. This could be concluded that LNP gene might involve in MDK pathogenesis. This finding could be a clue for extensive study to determine the mechanism causing mesomelic dysplasia, Kantaputra type.