Certain genetic variations within the TPMT gene can lead to decreased or absent TPMT enzyme activity, and individuals who are homozygous or heterozygous for these types of genetic variations may have increased levels of TGN metabolites and an increased risk of severe bone marrow suppression (myelosuppression) when receiving azathioprine. In many ethnicities, TPMT polymorphisms that result in decreased or absent TPMT activity occur with a frequency of approximately 5%, meaning that about 0.25% of patients are homozygous for these variants. However, an assay of TPMT activity in red blood cells or a TPMT genetic test can identify patients with reduced TPMT activity, allowing for the adjustment of azathioprine dose or avoidance of the drug entirely. The FDA-approved drug label for azathioprine recommends testing for TPMT activity to identify patients at risk for myelotoxicity. Indeed, testing for TPMT activity is one of the few examples of pharmacogenetics being translated into routine clinical care. Missense SNP in NUDT15 (e.g., rs116855232, inducing R139C)) has been identified to be a causal factor for AZA-induced leukopenia through a genome wide association study (GWAS) in East Asians. Cancers
Azathioprine is listed as a human carcinogen in the 12th Report on Carcinogens by the National Toxicology Program of U.S. Department of Health and Human Services, asserting that it is "known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans."
1p36 deletion syndrome  is a congenital genetic disorder characterized by moderate to severe intellectual disability, delayed growth, hypotonia, seizures, limited speech ability, malformations, hearing and vision impairment, and distinct facial features. The symptoms may vary, depending on the exact location of the chromosomal deletion.The condition is caused by a genetic deletion (loss of a segment of DNA) on the outermost band on the short arm (p) of chromosome 1. It is one of the most common deletion syndromes. It is estimated that the syndrome occurs in one in every 5,000 to 10,000 births. Signs and symptoms
There are a number of signs and symptoms characteristic of monosomy 1p36, but no one individual will display all of the possible features. In general, children will exhibit failure to thrive and global delays. Developmental and behavioral
Most young children with 1p36 deletion syndrome have delayed development of speech and motor skills. Speech is severely affected, with many children learning only a few words or having no speech at all. Behavioral problems are also common, and include temper outbursts, banging or throwing objects, striking people, screaming episodes, and self-injurious behavior (wrist biting, head striking/banging). A significant proportion of affected people are on the autism spectrum, and many exhibit stereotypy. Neurologic
Most people with 1p36 deletion syndrome have some structural abnormality of the brain, and approximately half have epilepsy or other seizures. Almost all children exhibit some degree of hypotonia. Common structural brain abnormalities include agenesis of the corpus callosum, cerebral cortical atrophy, gait abnormalities, and ventriculomegaly.