Detection of a Recurrent TMEM38B Gene Deletion Associated with Recessive Osteogenesis Imperfecta

Abstract

Osteogenesis imperfecta is a clinically and genetically group of heterogeneous disorders associated with decreased bone density, brittle bones, bone deformity, recurrent fractures, and growth retardation. Osteogenesis imperfecta is commonly associated with mutations of the genes encoding for type I collagen (COL1A1/COL1A2). Mutations in other genes, some associated with type I collagen post-translational processing, have also been identified as the cause of osteogenesis imperfecta. Mutations in the transmembrane protein 38B (TMEM38B) gene have been reported in a rare autosomal recessive form of osteogenesis imperfecta. TMEM38B encodes TRIC-B - a trimeric intracellular cation channel type B which is essential to modulate intracellular calcium signaling. In this study, we are reporting a case of osteogenesis imperfecta type XIV from a Saudi consanguineous family. Our patient was an eight-month-old child with short limbs, club feet, and lower limb deformities with developmental delay. Radiological findings were consistent with the evidence of osteogenesis imperfecta. There was no evidence of impaired hearing or blue sclera and based on the clinical assessment, we classified our patient as a non-syndromic osteogenesis imperfecta. A pathogenic deletion in the chromosome 9q31.2 region, partially encompassing the TMEM38B gene, was detected using chromosomal microarray analysis. This study expands our knowledge about the rare type of osteogenesis imperfecta in our consanguineous population. Besides, it emphasizes the use of genomic medicine in clinical practices to formulate early interventions to clinically improve the patient's condition.

Keywords: Osteogenesis imperfecta; mutations; recessive..

Figure 1. TMEM38B mutations associated with osteogenesis imperfecta type XIV

Figure 2. Clinical features of the patient with TMEM38B related phenotype

A. and B. Images of the lower extremities showing mild shortening and bowing. Bilateral talipes equinovarus deformity was observed; C. and D. Representative radiograms of a patient with TMEM38B at 8 months of age. Skull radiographs showing generalized osteopenia, thin cortex of calvarium, and thickening of the occipital part of the skull. Patent sutures with no evidence of Wormian bone. Lateral spine view of the whole body showing generalized osteopenia and normal shape and height of vertebrae with maintained disc space. Chest showing osteopenia, thin ribs, mild widening of the costochondral junctions of the dorsal ribs and decreased aeration of both lungs. Right upper limb radiograph showing opteopenia. Anteroposterior view of lower limbs showing significant bilateral bowing and femoral deformity. The bowing was more prominent in the lower extremities in a background of metaphyseal irregularity. Diffuse osteopenia and healed fracture of the distal left femoral metaphysis were noted.