scholarly journals Point mutagenesis in mouse reveals contrasting pathogenetic effects between MEN2B‐ and Hirschsprung disease‐associated missense mutations of the RET gene

2020 ◽  
Vol 62 (4) ◽  
pp. 214-222
Author(s):  
Taichi Nakatani ◽  
Mitsuhiro Iwasaki ◽  
Atsuhiro Yamamichi ◽  
Yuta Yoshioka ◽  
Toshihiro Uesaka ◽  
...  
Keyword(s):  
Hirschsprung Disease ◽  
Missense Mutations ◽  
Ret Gene ◽  
Point Mutagenesis

scholarly journals A human model for multigenic inheritance: Phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus

2000 ◽  
Vol 97 (1) ◽  
pp. 268-273 ◽  
Author(s):  
S. Bolk ◽  
A. Pelet ◽  
R. M. W. Hofstra ◽  
M. Angrist ◽  
R. Salomon ◽  
...  
Keyword(s):  
Phenotypic Expression ◽  
Hirschsprung Disease ◽  
Human Model ◽  
Ret Gene

scholarly journals Goldberg-Shprintzen Syndrome Associated with a Novel Variant in the KIFBPGene

2021 ◽  
pp. 1-4
Author(s):  
Pelin Ozyavuz Cubuk
Keyword(s):  
Developmental Delay ◽  
Clinical Features ◽  
Hirschsprung Disease ◽  
Missense Mutations ◽  
Dysmorphic Features ◽  
Brain Anomalies ◽  
Responsible Gene ◽  
Novel Variant ◽  
Exome Analysis ◽  
Kinesin Family

Goldberg-Shprintzen syndrome (GOSHS) is characterized by microcephaly, developmental delay, dysmorphic features, Hirschsprung disease (HSCR), and brain anomalies. The kinesin family binding protein (<i>KIFBP</i>; MIM 60937) gene has been identified as the responsible gene of the syndrome. To date, 16 different biallelic <i>KIFBP</i> mutations have been identified in 34 patients with GOSHS. Even though most of these mutations are nonsense and frameshift, 3 missense mutations have also been described. Here, we report an 18-month-old patient with microcephaly, developmental delay, dysmorphic features and HSCR. Exome analysis was performed to clarify the etiology of the clinical features. A previously unreported homozygous c.1723delC (p.H575Ifs*19) variant was detected in the last exon 7 of <i>KIFBP</i> which led to GOSHS. According to our findings, we suggest that this mutation expands mutational databases and contributes to the understanding of the phenotypic features of the syndrome.

scholarly journals Bioinformatics methods for identifying Hirschsprung disease genes

2021 ◽  
Vol 9 (VII) ◽  
pp. 2974-2978
Author(s):  
Sudheer Menon
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Protein Function ◽  
Birth Defect ◽  
Human Genetics ◽  
Hirschsprung Disease ◽  
Enteric Neurons ◽  
Disease Genes ◽  
Common Cause ◽  
Ret Gene

Hirschsprung is a birth defect of Enteric Nervous System (ENS) which is characterized by the absence of enteric neurons along the length of intestine. Hirschsprung is one of the complex diseases which has become a important topic of human genetics. In this article we have focused on RET gene mutation that is most common cause of HSCR disease. Out of seven mutations in RET gene, one mutation S339L is found to be tolerated and have no effect on protein function.

scholarly journals Common PHOX2B poly-alanine contractions impair RET gene transcription, predisposing to Hirschsprung disease

2017 ◽  
Vol 1863 (7) ◽  
pp. 1770-1777 ◽  
Author(s):  
Eleonora Di Zanni ◽  
Annalisa Adamo ◽  
Elga Belligni ◽  
Margherita Lerone ◽  
Giuseppe Martucciello ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Hirschsprung Disease ◽  
Ret Gene

scholarly journals SRY interference of normal regulation of the RET gene suggests a potential role of the Y-chromosome gene in sexual dimorphism in Hirschsprung disease

2014 ◽  
Vol 24 (3) ◽  
pp. 685-697 ◽  
Author(s):  
Yunmin Li ◽  
Tatsuo Kido ◽  
Maria M. Garcia-Barcelo ◽  
Paul K. H. Tam ◽  
Z. Laura Tabatabai ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Y Chromosome ◽  
Potential Role ◽  
Hirschsprung Disease ◽  
Ret Gene ◽  
Chromosome Gene

Genetic mosaicism of a frameshift mutation in the RET gene in a family with Hirschsprung disease

Gene ◽  
2014 ◽  
Vol 541 (1) ◽  
pp. 51-54 ◽  
Author(s):  
Charlotte M. Müller ◽  
Michael G. Haase ◽  
Ivonne Kemnitz ◽  
Guido Fitze
Keyword(s):  
Frameshift Mutation ◽  
Hirschsprung Disease ◽  
Ret Gene ◽  
Genetic Mosaicism

Screening of the RET gene of Vietnamese Hirschsprung patients identifies 2 novel missense mutations

2012 ◽  
Vol 47 (10) ◽  
pp. 1859-1864 ◽  
Author(s):  
Diem-Ngoc Ngo ◽  
Man-Ting So ◽  
Hongsheng Gui ◽  
Anh-Quynh Tran ◽  
Duc-Hau Bui ◽  
...  
Keyword(s):  
Missense Mutations ◽  
Ret Gene

scholarly journals Exome sequencing identified a novel pathogenic RET variant with high variable expressivity and incomplete penetrance in an extended pedigree with Hirschsprung disease

2020 ◽  
Author(s):  
Sahereh Rahnavard ◽  
maryam eghbali ◽  
hassan saei ◽  
bahar Ashjaei ◽  
maryam abiri
Keyword(s):  
Exome Sequencing ◽  
Chronic Constipation ◽  
Extended Family ◽  
Hirschsprung Disease ◽  
Incomplete Penetrance ◽  
Extended Pedigree ◽  
Ret Gene ◽  
Wide Range ◽  
The Family ◽  
Single Kidney

Abstract Background: Hirschsprung disease (HSCR) is a developmental disorder characterized by the absence of ganglion cells in the gastrointestinal tract, which consequences in intestinal obstruction. HSCR has more than 80% heritability, including two major forms as sporadically which is the most common form with a complex pattern of inheritance and other forms appear with a familial/syndromic basis along with Mendelian inheritance and incomplete penetrance. The rare and common sequence variants in genes related to the enteric nervous system (ENS) was identified to play a critical role in the progress of HSCR. Results: This study aimed to investigate the genetic basis of an Iranian extended family with different manifestations such as inherited HSCR, chronic constipation, congenital malformations (single kidney and closed anus) to find the causal mutations. To uncover the contributing genetic variant/s, exome sequencing was performed on proband (IV-V). Finally, with the standard filtering protocol, we identified a novel heterozygous nonsense mutation, p.Y314X at exon 5 of the RET gene. This variant is located in the extracellular domain of RET tyrosine kinase and subsequently leads to no detectable RET full-length protein and so may lead to protein loss of function. This devastating variant is manifested in the proband, with long‐segment form and other phenotypes such as single kidney, absent of peritoneum and pigmentation of the face. However, this variant has been segregated in the mother (III-IV, with single kidney), the grandmother (II-II, with diarrhea) and the aunt (III-V, with chronic constipation and premature ovarian failure); these members of the family didn’t show HSCR. Furthermore, in other members of the family (II-IV and III-XII) with chronic constipation and no HSCR, the variant was detected. Nonetheless, this phenomenon can be interpreted by incomplete or reduced penetrance in this extended family with variable expression. Conclusions: The present study found a novel null variant at RET gene that is associated with a wide range of phenotypes and incomplete penetrance. This can be synergistic effects of rare and/or common variants among known and/or unknown disease susceptibility genes which lead to variable severity of phenotype. Such information is important for proper genetic counseling in familial HSCR. Keywords : Hirschsprung disease, whole-exome sequencing, RET novel mutation, extended pedigree, incomplete penetrance.

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