New mutations associated with Hirschsprung disease

Lorente-Ros, Marta; Andrés, Ane Miren; Sánchez-Galán, Alba; Amiñoso, Cinthia; García, S. García; Lapunzina, Pablo; Solera-García, Jesús

doi:10.1016/j.anpede.2019.05.007

Cited by 2 publications

(1 citation statement)

References 18 publications

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“…These are often Gastrointestinal anomalies (intestinal malrotation, imperforate anus), genitourinary anomalies (cryptorchidism, inguinal hernia, hypospadias, renal malformation), cardiac anomalies (such as atrial septal defect, ventricular septal defect, patent ductus arteriosus, tetralogy of Fallot), and central nervous system anomalies (intellectual disability and microcephaly) (41). In this study, in addition to HSCR, the history of the family was shown other manifestations/malformations such as single kidney, closed anus, premature ovarian failure, chronic constipation, and so on.…”

Section: Discussionmentioning

confidence: 99%

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

Rahnavard¹,

Eghbali-Babadi²,

Saei³

et al. 2020

Preprint

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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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Section: Discussionmentioning

confidence: 99%

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

Rahnavard¹,

Eghbali-Babadi²,

Saei³

et al. 2020

Preprint

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Effect of Transumbilical Single-Port Laparoscopic-Assisted Duhamel Operation on Serum CRP and IL-6 Levels in Children with Hirschsprung’s Disease

Wang

Pang

Zhang

et al. 2022

Journal of Healthcare Engineering

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Objective. To explore the clinical intervention effect of transumbilical single-port laparoscopic-assisted Duhamel operation on children with Hirschsprung’s disease (HD) and to analyze the effect of treatment on children with serum C-reactive protein (CRP) and interleukin-6 (IL-6) effects. Methods. Retrospectively select 80 children with HD who underwent surgery in our hospital from May 2017 to May 2020 as the research subjects and they are classified as group A according to the difference of the children’s surgical procedures (receiving transumbilical single-port laparoscopic-assisted Duhamel surgery, 40 cases) and group B (receiving conventional laparoscopic surgery, 40 cases), compare the perioperative period (operating time, intraoperative blood loss, surgical posthospitalization, and postoperative gastrointestinal function recovery time), early postoperative complications (perianal dermatitis, urinary retention, enterocolitis, and anastomotic leakage), and late postoperative complications (anastomotic stenosis, dirty stool, recurrence of constipation, and enterocolitis), compare the differences in the levels of CRP and IL-6 between the two groups of children before and after the operation, and conduct a 1-year follow-up of the two groups of children to compare the long-term defecation status. Results. The surgical time of children in group A, postoperative hospitalization time, and postoperative gastrointestinal function recovery time were significantly shorter than those of group B, and the differences between groups were statistically significant ( P < 0.05 ). A group of patients: the total incidence of postearly complications was 5.00% lower than 22.50% ( P < 0.05 ) in group B ( P < 0.05 ), and the total incidence of previous complications after group A of patients was 10.00% lower than 27.50% of group B ( P < 0.05 ). The two groups of serum CRP and IL-6 in two groups were not statistically significant ( P > 0.05 ), and the serum CRP and IL-6 levels of children in group A after surgery were 3 days. It is obviously lower than those in group B, and the differences between groups have statistical significance ( P < 0.05 ). At 1 month after surgery, the average bowel movement time in group A is significantly lower than those of group B ( P < 0.05 ); during the 1–12 months, the difference between the defecation frequency group of the group A and group B did not have statistically significance ( P > 0.05 ). Conclusion. Transumbilical single-port laparoscopic assistant Duhamel operation of HD has a good intervention effect, compared to traditional laparoscopic surgery, the operation time, postoperative hospitalization time, and postoperative gastrointestinal function recovery time, and also help to reduce postoperative near-long complications The incidence improves the stress reactions and long-term defecation functions in children.

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New mutations associated with Hirschsprung disease

Cited by 2 publications

References 18 publications

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

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

Effect of Transumbilical Single-Port Laparoscopic-Assisted Duhamel Operation on Serum CRP and IL-6 Levels in Children with Hirschsprung’s Disease

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