Which gene mutation leads to adrenal crisis in neonates due to ACTH deficiency?

The mutation in the pro-opiomelanocortin (POMC) gene is responsible for adrenal crisis in neonates as it directly affects the production of several important hormones, including adrenocorticotropic hormone (ACTH). POMC is a precursor polypeptide that is cleaved to produce several peptides, one of which is ACTH. In the case of POMC deficiency, there is inadequate ACTH production, which in turn leads to insufficient stimulation of the adrenal glands to produce cortisol. This deficiency can result in adrenal insufficiency, particularly in neonates, and can manifest as an adrenal crisis, characterized by severe fatigue, low blood pressure, and the potential for life-threatening electrolyte imbalances.

The other options do not directly relate to ACTH deficiency. The leptin gene is involved in regulating energy balance and appetite, the MC4R gene is implicated in pathways related to obesity and energy homeostasis, and the insulin gene is crucial for glucose metabolism and not directly involved with ACTH or adrenal function. Therefore, the mutation in the POMC gene is specifically linked to the deficiency and subsequent adrenal crisis in neonates due to its critical role in stimulating hormone production essential for adrenal function.