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Megacystis microcolon intestinal hypoperistalsis syndrome
Published in Prem Puri, Newborn Surgery, 2017
Prem Puri, Jan-Hendrik Gosemann
The evaluation of the genetic background of MMIHS resulted in a number of recent publications that suggest the enteric smooth muscle actin gamma 2 (ACTG2) as the first gene to be clearly associated with MMIHS 15–17 and intestinal pseudo-obstruction. Some authors suggest to reorganize the clinical entities of MMIHS, prune belly syndrome, hollow visceral myopathy, and intestinal pseudo-obstruction into a spectrum of ACTG2-related disorders.15 The identification of a possible genetic background might have a relevant impact on prenatal counselling in the future.
Leiomyosarcoma
Published in Dongyou Liu, Tumors and Cancers, 2017
The MYOCD gene (on 17p12) encodes myocardin (MYOCD), a transcriptional cofactor of serum response factor, that regulates smooth muscle differentiation and cell migration. It is the most overexpressed in leiomyosarcomas of the retroperitoneum. Further, gains at 1q21.3, 11q12.2-q12.3, 16p11.2, and 19q13.12 correlate to increased risk of death. Some leiomyosarcomas demonstrate high expression levels of muscle-associated genes, including CALD1, SLMAP, ACTG2, CFL2, MYLK, ACTA2, MBNL1, TPM1, PPP1R12A, DTNA, FZD6, PPP1R12A, CLIC4, CDC42EP3, BARD1, TPM1, RAB27A, MAP1B, and EDIL [4,5].
Five New Cases of Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome (MMIHS), with One Case Showing a Novel Mutation
Published in Fetal and Pediatric Pathology, 2021
Alyssa Kalsbeek, Renee Dhar-Dass, Abdul Hanan, Eman Al-Haddad, Iman William, Adina Alazraki, Janet Poulik, Kasey McCollum, Aya Almashad, Bahig M. Shehata
We had one case of a missense mutation in ATP2B4 on Chromosome 1q32. This patient had a milder course with a delayed presentation at 11 months and the longest survival with the aid of multi-organ transplantation. These results seem to indicate that this infant presented with sporadic MMIHS. Familial forms of MMIHS are more often associated with high frequency polymorphisms in CHRNA3 and CHRNAB4 genes, which differ from the way in which the identified sporadic missense mutation in the genes ACTG2 and ATP2B4 lead to MMIHS. The differences in the molecular genetic basis between familial and sporadic forms of MMIHS are still being explored with varying hypothesis being studied. In another study on sporadic MMIHS, it was proposed that ACTG2 variants lead to the phenotypic expression of MMIHS [24]. The results of our study in the ACTG2 gene, but instead a different missense mutation which regulates calcium transport in the plasma membrane. Additional investigation is needed to explore the relationship between ATP2B4 gene mutations and MMIHS. These sporadic cases of MMIHS suggest that missense mutations may not lead to complete loss of function of the plasma membrane ATPase, which may also be related to clinically milder visceral myopathies, and better outcomes following multi-organ transplantation. This should be considered when forming a prognosis and treatment plan. Histologic findings from patients with MMIHS have shown vacuolar degeneration of smooth muscle cells, reactive interstitial fibrosis, and decreased staining of smooth muscle actin in the circular layer of the small bowel [17,24–26].
Targeting glucose-dependent insulinotropic polypeptide receptor for neurodegenerative disorders
Published in Expert Opinion on Therapeutic Targets, 2018
Mahip K. Verma, Rajan Goel, Nandakumar Krishnadas, Kumar V. S. Nemmani
GIP-mediated rescue of the CGNs associates with the upregulation of zinc and ring finger 1 E3 ubiquitin protein ligase (Znrf1) and ubiquitin specific peptidase 10 (Usp10) [48]. Znrf1 ubiquinates GLUL and AKT1, playing a critical role in the neuronal differentiation, neurotransmission, and synaptic plasticity [60]. Usp10 is a deubiqutinating hydrolase that removes the ubiquitin from host of molecules, namely, p53, CFTR, SNX3, and BECN1, regulating the DNA-damage response in mammalian cells [61]. Treatment with GIP led to differential expression (over-expression) of genes involved in the cytoskeletal machinery, e.g. Actin beta (Actb) and Actin, gamma 2, smooth muscle, enteric (Actg2) [48]. Actb is involved in cell mobility, neuronal plasticity, and neuroprotective effects in prospinal neurons [62]. Actg2 regulates the motility of neurons along with cytoskeletal organization and maintenance [63].
Megacystis Microcolon Intestinal Hypoperistalsis Syndrome in Which a Different De Novo Actg2 Gene Mutation was Detected: A Case Report
Published in Fetal and Pediatric Pathology, 2018
Elif Ünver Korğalı, Amine Yavuz, Cemile Ece Çağlar Şimşek, Cengiz Güney, Hande Küçük Kurtulgan, Burak Başer, Mehmet Haydar Atalar, Hatice Özer, Hatice Reyhan Eğilmez
Although most MMIHS occur sporadically, there are familial cases. In these familial cases the heterozygous mutation in the ACTG2 gene on chromosome 2p13 has an autosomal dominant inheritance. There is inter- and intrafamilial variability (12). Heterozygous de novo changes on ACTG2 gene in sporadic cases have been reported in recent studies. It is thought that these changes in the ACTG2 gene, which encodes one of the six actin isoforms in smooth muscle cells in human gastrointestinal and urinary systems, are responsible for the hypoperistalsis in MMIHS patients (13–16). The c.532C>A /p.Arg178Ser heterozygous de novo ACTG2 gene mutation detected in the current patient is a new mutation reported for the first time in MMIHS patients. In 2014, Thorson et al. defined c.532C>T/p.R178C de novo mutation in the same location (14). They reported that this mutation is a pathogenic gene change responsible for MMIHS in their patient. In the current patient, it was also considered that the c.532C>A /p.Arg178Ser heterozygous de novo change was responsible in the pathogenesis of MMHIS. This new mutation is deleterious with a −4.78 provean score (http://provean.jcvi.org/genome_submit_2.php) and probably damaging with a 0.909 score of polyphen2 (http://genetics.bwh.harvard.edu/pph2/). Therefore, this new mutation was predicted to be pathogenic (disease causing mutation) by mutation taster (http://www.mutationtaster.org/). The provision of genetic counseling was planned for the family for future infants considering the possibility that this change could show gonadal mosaicism (16).