Hirschsprung disease is due to (AIIMS NOV 2009)
|A||Loss of ganglion cells in sympathetic chain|
|B||Failure of migration of neural crest cells from cranial to caudal direction|
|C||Atrophy of longitudinal muscles|
|D||Loss of vagal innervation of myenteric plexus|
I. Hirschsprung's disease, or congenital aganglionic megacolon, involves an enlargement of the colon, caused by bowel obstruction resulting from absence of normal peristaltic activity Q.
II. According to latest research, Hirschsprung's is caused by the interaction between two proteins encoded by two variant genes. The RET proto-oncogene on chromosome 10 was identified as one of the genes involved Q.
III. The protein with which RET has to interact in order for Hirschsprung’s disease to develop is termed EDNRB and is encoded by the gene EDNRB located on chromosome 13.
IV. The authors conclude that the mode of inheritance for Hirschsprung’s is oligogenic. This means that two mutated genes interact to cause a disorder. Variations in RET and EDNRB have to coexist in order for a child to get Hirschsprung’s.
V. RET codes for proteins that assist cells of the neural crest Q (which later become ganglion cells) in their movement through the digestive tract during the development of the embryo from cranial to caudal direction. EDNRB codes for proteins that connect these nerve cells to the digestive tract.