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Central nervous system: Adult-onset and psychiatric disorders
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Hereditary benign chorea is characterised by non-progressive chorea present from infancy, without mental retardation. Inheritance is autosomal dominant, with reduced penetrance in females. It is most important not to confuse this benign condition with HD. It is usually caused by a specific mutation in NKX2-1 and represents the mildest of the wide range of phenotypes associated with mutations in this gene (that can also affect the thyroid gland and the lung).
Islet Transplantation in Type 1 Diabetes: Stem Cell Research and Therapy
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
After the pancreatic epithelium growth and proliferation, Notch signaling is inhibited in some epithelial cells, allowing the expression of pro-endocrine gene Neurogenin-3 (Ngn3) [35]. Ngn3 is expressed in all endocrine progenitor cells, which initiates a cascade of transcription factor expression which, in turn, initiates differentiation of endocrine cells. This cascade includes Nkx2-2, Neurod–1, Nkx6-1, Pax6, Pax4, and Isl1.
Infantile hypertrophic pyloric stenosis
Published in Prem Puri, Newborn Surgery, 2017
Prem Puri, Balazs Kutasy, Ganapathy Lakshmanadass
Although a specific gene responsible for IHPS has not yet been discovered, several susceptible loci have been identified, such as 3p25, 16p12-q13, 16q14, 11q14-q22, 11q23, and Xq23 involving NOS1, APOA1, NKX2-5, and MBNL1 genes.35–39 In view of the implication of the enzyme neuronal nitric oxide synthase (nNOS) in the pathogenesis of IHPS, NOS1, the gene encoding nNOS on chromosome 12q, has been investigated by linkage analysis and evaluation of nNOS mRNA expression40 and suggested as a susceptibility locus. APOA1 encodes apolipoprotein A-1, a major protein component of high-density lipoprotein (HDL) in plasma, which has been found to be associated with levels of circulating cholesterol.37 In IHPS, lower cholesterol levels have been found at birth in infants who went on to develop IHPS compared with matched controls who did not develop the disease.37 A number of previous findings would be consistent with low lipid levels representing an important risk factor for IHPS: The protective effect of female sex could at least partly be due to higher cholesterol levels, since it is well known that levels of LDL cholesterol and HDL cholesterol are, on average, higher in newborn girls compared to boys; IHPS risk associated with bottle-feeding could in part be caused by insufficient lipid levels since bottle-feeding is known to be associated with lower total and LDL cholesterol levels in infancy; and cholesterol has an essential role in nervous system including enteric nervous system development.37 NKX2-5 encodes the NK2 homeobox 5 transcription factor, which has been shown to have a critical role in pyloric sphincter development.39,41,42 It has been reported that Sox9 is critical for embryonic pyloric smooth muscle development.41,42 Nkx2-5 and Gata3 are required for pyloric sphincter morphogenesis, and both directly or indirectly regulate Sox9.42,43 It has been suggested that some forms of IHPS can result from overexpression of NKX2-5 at the pylorus.42 MBNL1 is a double-stranded RNA binding protein, and it is a member of muscleblind protein family, which are important regulators of alternative splicing.38,39 In the early postnatal period, splicing transitions from fetal to adult protein isoforms are essential for the extensive remodeling of muscle tissue that occurs as a part of normal development.44 In studies of mouse heart and skeletal muscle development, Mbnl1 has been shown to control a set of temporally correlated splicing transitions that occur within the first 3 weeks of postnatal life.45,46 The intriguing observation that IHPS occurs almost exclusively between 2 and 8 weeks after birth points to a possible role for misregulation of MBNL1 controlled splicing transitions in the etiology of IHPS.38
Chronic interstitial lung diseases in children: diagnosis approaches
Published in Expert Review of Respiratory Medicine, 2018
Nadia Nathan, Laura Berdah, Keren Borensztajn, Annick Clement
Lung disorder resulting from NKX2-1 dysfunction was first reported in an infant with neonatal thyroid disease and respiratory failure [83]. It has since been associated with the ‘brain-lung-thyroid’ syndrome. The inheritance pattern is autosomal dominant, with incomplete penetrance and severity for each of the 3 involved organs, even in a single family [84]. Approximately half of the mutations are de novo mutations. NKX2-1 is a transcription factor, located on chromosome 14, that promotes SFTPB, SFTPC and ABCA3 transcription in the alveolar epithelial cells. To date, over 50 mutations have been described, with no recurrent mutation identified [85].
The role of stem cells in cystic fibrosis disease modeling and drug discovery
Published in Expert Opinion on Orphan Drugs, 2018
Massimo Conese, Elisa Beccia, Annalucia Carbone, Stefano Castellani, Sante Di Gioia, Fabiola Corti, Antonella Angiolillo, Carla Colombo
McCauley et al. [55] purified NKx2-1+ primordial lung progenitors using the cell surface markers CD47 and CD26 to isolate CD47hiCD26− cells highly enriched in NKx2-1+ progenitors by day 15 from one CF and two CF cell lines [60]. With time-lapse microscopy of non CF-derived organoids after exposure to forskolin, swelling was detected. By contrast, little, if any, swelling was observed in two iPSC-derived CF lines after exposure to forskolin.
Clinicopathological indicators of survival among patients with pulmonary carcinoid tumor
Published in Acta Oncologica, 2018
Tiina Vesterinen, Sanna Mononen, Kaisa Salmenkivi, Harri Mustonen, Ilkka Ilonen, Aija Knuuttila, Caj Haglund, Johanna Arola
Thyroid transcription factor-1 (TTF-1) belongs to the NKX2 gene family. It plays a role in normal lung development but also contributes to the pathogenesis of lung cancer [16]. Studies show TTF-1 expression in a significant subset of PCs, but to our knowledge, reports on its correlation to survival are limited [17–19].