Molecular characteristics
PTPN23 (Protein-Tyrosine Phosphatase, Nonreceptor-Type, 23) gene is located at 3p21.31. Little is known about PTPN23. There is a predominant expression of PTPN23 in the CNS, especially in the neuroepithelial lining of the hindbrain and midbrain and at the inner side of the otic and optic vesicles in the ventricular layer of the forebrain in mice. Haploinsufficiency of PTPN23 predisposes to sporadic B cell lymphoma and lung adenoma. PTPN23 interacts and interferes with survival motor neuron protein (SMN) accumulation in Cajal bodies, is involved in the modulation of SMN complex formation, and may play an essential role in motor neurones. It plays a role in ciliogenesis and may act as a negative regulator of Ras-mediated mitogenic activity.
Mutations and pathophysiology
PTPN23 mutations cause an autosomal recessive form of developmental and epileptic encephalopathy. Dr. Helly Goez (personal communication) identified a compound heterozygous mutation in PTPN23: c.3905dup leading to p.(Tyr1302*). The patient was born to non-consanguineous parents. The patient displayed mildly delayed gross motor milestones for the first 6 months of life followed by developmental regression, which initially affected eye tracking and focusing, visual attention, and gross motor skills. This was followed by a regression in fine motor skills, language, social skills, and swallowing. The other clinical features were consistent with PTPN23-related disorder phenotype described in the Professionals – Clinical characteristics section.
Selected examples from the literature are described below:
- Sowada et al. (2017) reported a compound heterozygous mutation in PTPN23: c.3586C>T (p.Arg1196*) nonsense and c.1595C>T (p.Pro532Leu) missense mutations. The affected patient was born to non-consanguineous German parents and displayed the phenotypical features of the disorder. The patient died of pneumonia at the age of 4 years and 10 months.
- Alazami et al. (2015) reported a homozygous mutation in PTPN23, c.3995G>T leading to p.Arg1332Leu. The affected patient came from a Saudi consanguineous family.
- Trujillano et al. (2017) identified a homozygous mutation in PTPN23, c.904A>G leading to p.Met302Val. The affected patient displayed symptoms consistent with the disorder, including global developmental delay, brain atrophy, microcephaly, and seizures.