To date two siblings are both compound heterozygous for a paternally inherited c.888 +1 G>A mutation and a maternally inherited p.N131S mutation. Another child has been identified with compound heterozygous c.912_917delTTACAT, p.Y305_I306del and p.N131S mutations in DHPS. The fact that all three children share the p.N131S mutation with a loss of function mutation suggests that it is extremely likely that this is the correct diagnosis.
We have studied the c.888 +1 G>A mutation and have demonstrated that it results in abnormal splicing of the DHPS gene and leads to loss of function of that copy of the DHPS gene. The p.Tyr305_Ile306del mutation present in the third child is also very likely to lead to loss of function of the DHPS gene. We need to do additional experimental studies on the p.N131S mutation to determine what effect it has on DHPS. It is possible that it leads to decreased but not complete loss of DHPS.