In the 5 years since the discovery of PTEN, encoding a dual specificity phosphatase tumor suppressor on 10q23, it has been shown to be a susceptibility gene for an inherited cancer syndrome, Cowden syndrome, and for several developmental disorders; it has been shown to play a prominent role in normal murine and human development; and it has been shown to be instrumental in cell cycle arrest, apoptosis, and/or possibly cell migration and cytoskeletal affairs.
Rett syndrome (RTT) is one of the most common causes of intellectual and developmental disabilities in girls, and is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MECP2).
Methyl-CpG-binding protein 2 (MECP2) deleterious variants, which are responsible for Rett syndrome in girls, are involved in a wide spectrum of developmental disabilities in males.
Numerous mutations in DNMTs, TETs and MeCP2 have been identified in cancer and developmental disorders, highlighting the importance of the DNA methylation machinery in human development and physiology.
The FOXG1 gene was sequenced in 210 patients, including 129 patients with unexplained developmental disorders and 81 MECP2 mutation negative individuals.
Mutations in MECP2 gene account for approximately 80% of cases of Rett syndrome (RTT), an X-linked severe developmental disorder affecting young girls, as well as for most cases of Preserved Speech Variant (PSV), a mild RTT variant in which autistic behavior is common.
Mutations of SETD1A have been implicated in schizophrenia and developmental disorders, so we examined the role of the four mutations (R913C, Q269R, G1369R, and R1392H) in neural development.
We further identified four SETD1A LoF carriers among 4,281 children with severe developmental disorders and two more carriers in an independent sample of 5,720 Finnish exomes, both with notable neuropsychiatric phenotypes.
Therefore, we think it is crucial to look for mutations in the gene SHANK3 in patients diagnosed for childhood disintegrative disorder or any developmental disorder with a regressive pattern involving social and communicative skills as well as cognitive and instinctual functions, with onset around 3 years.
Haploinsufficiency of the SHANK3 gene causes a developmental disorder, 22q13.3 deletion syndrome (known as Phelan-McDermid syndrome), that is characterized by severe expressive language and speech delay, hypotonia, global developmental delay, and autistic behavior.
Urine screening for patients with developmental disabilities detected a patient with creatine transporter deficiency due to a novel missense mutation in SLC6A8.