FIGURE 4.

The proposed molecular diagnostic procedure to identify the genetic etiology of critically ill patients from NICUs. CAH, congenital adrenal cortical hyperplasia; CMA, chromosomal microarray analysis; DMD, Duchenne muscular dystrophy; MLPA, multiplex ligation-dependent probe amplification; TES, targeted exome sequencing; WES, whole-exome sequencing. The reference clinical phenotypes includes complex metabolic phenotypes (e.g., persistent hypoglycemia, hyperkalemia, hyponatremia, metabolic acidosis, lactic acidosis, and hyperammonemia); unexplained neurological signs (e.g., seizures and hypotonia); unexplained respiratory failure; unexplained abnormalities of the cardiovascular system (e.g., cardiomyopathy and arrhythmia); skin lesions of unknown origin(e.g., ichthyosis and blister); unexplained thrombocytopenia or anemia; congenital malformations that are not consistent with any known syndrome; unexplained abnormalities of the immune system(e.g., recurrent infections, protracted diarrhea, leukocytosis, leukopenia, and abnormal immunoglobulin level); unexplained cholestasis.