A gene for Hirschsprung disease maps to the proximal long arm of chromosome 10

Lyonnet, Stanislas; Bolino, Alessandra; Pelet, Anna; Abel, Laurent; Nihoul‐Feketé, Claire; Briard, Marie-Louise; Mok-Siu, V.; Kääriäinen, Helena; Martucciello, G.; Lerone, Margherita; Puliti, Aldamaria; Yin, Ling; Weissenbach, Jean; Devoto, Marcella; Münnich, Arnold; Romeo, Giovanni

doi:10.1038/ng0893-346

Cited by 183 publications

(79 citation statements)

References 36 publications

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“…It is the most common cause of neonatal intestinal obstruction, affecting one in 5,000 live newborns with a male predominance (3:1-5:1) (Angrist et al 1993;Badner et al 1990;Lyonnet et al 1993;Reyna 1993). The phenotype in HSCR can be classified into two groups: short-segment aganglionosis (SSA), which includes patients with aganglionosis as far as the rectosigmoid junction, and long-segment aganglionosis (LSA), which includes patients with aganglionosis beyond the rectosigmoid junction and total colon or universal intestinal aganglionosis (TCA) (Reyna 1993).…”

Section: Introductionmentioning

confidence: 99%

Low RET mutation frequency and polymorphism analysis of the RET and EDNRB genes in patients with Hirschsprung disease in Taiwan

Tsai

Chu

et al. 2005

J Hum Genet

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Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a relatively common disorder characterized by the absence of ganglion cells in the nerve plexuses of the lower digestive tract, resulting in intestinal obstruction in neonates. Mutations in genes of the RET receptor tyrosine kinase and endothelin receptor B (EDNRB) signaling pathways have been shown to be associated in HSCR patients. In this study, we collected genomic DNA samples from 55 HSCR patients in central Taiwan and analyzed the coding regions of the RET and EDNRB genes by PCR amplification and DNA sequencing. In the 55 patients, an A to G transition was detected in two (identical twin brothers). The mutation was at the end of RET exon 19 at codon 1062 (Y1062C), a reported critical site for the signaling pathways. Single nucleotide polymorphisms (SNP) in exons 2, 7, 11, 13, and 15 of RET and exon 4 of EDNRB in the HSCR patients or controls were detected. The differences between patients and controls in allele distribution of the five RET polymorphic sites were statistically significant. The most frequent genotype encompassing exons 2 and 13 SNPs (the polymorphic sites with the highest percentage of heterozygotes) was AA/GG in patients, which was different from the AG/ GT in the normal controls. Transmission disequilibrium was observed in exons 2, 7, and 13, indicating nonrandom association of the susceptibility alleles with the disease in the patients. This study represents the first comprehensive genetic analysis of HSCR disease in Taiwan.

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Section: Introductionmentioning

confidence: 99%

Low RET mutation frequency and polymorphism analysis of the RET and EDNRB genes in patients with Hirschsprung disease in Taiwan

Tsai

Chu

et al. 2005

J Hum Genet

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“…It is characterized by a variable pattern of inheritance which has not yet been fully explored. Genes with a crucial role in the pathogenesis of HD include RET [12], Endothelin B receptor [13] and SOX [14]. Comorbidities such as Waardenburg syndrome, MEN2, Mowat-Wilson Syndrome, Down Syndrome and other chromosomal anomalies have been reported [15].…”

Section: Discussionmentioning

confidence: 99%

Phenylketonuria and Hirschsprung Disease—A Report of an Unusual Neonatal Presentation

Lenherr

Pfeifle

Holland‐Cunz

et al. 2017

IJNS

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Abstract:We describe a term born boy of non-consanguineous Swiss parents with tetrahydrobiopterine (BH 4 )-responsive Phenylketonuria (PKU) and Hirschsprung disease with unusual neonatal presentation. The child presented with floppiness, irritability, recurrent bilious vomiting and failure to pass meconium until 32 hours after birth, resulting in the clinical suspicion of an intoxication-type metabolic disease such as maple syrup urine disease (MSUD). Although the slightly elevated branched-chain amino acids in newborn screening on the fourth day of life initially supported the clinical suspicion of MSUD, the elevated Phenylalanine (Phe) of 650 µmol/L, low Tyrosine (Tyr) of 30 µmol/L, and a Phe/Tyr ratio of 22, led to the diagnosis of PKU. BH 4 -testing resulted in a significant decrease of Phe from 1011 to 437 µmol/L within 24 h. Urinary pterins and dihydropteridine reductase (DHPR) activity were normal, supporting the diagnosis of BH 4 -responsive PKU. Dietary restriction of Phe was initiated immediately, but oral feeding turned out to be difficult because of gastrointestinal symptoms. Intestinal motility disorder was suspected due to distended abdomen, obstructive symptoms and radiological findings with dilated intestinal loops and lack of intestinal gas in the anorectal region. Hirschsprung disease was confirmed by rectal suction biopsies and treated by a laparoscopically-assisted transanal pull-through (de la Torre) procedure. The boy is additionally compound heterozygous for two mutations in the phenylalanine hydroxylase (PAH) gene, which confirmed BH 4 -responsive PKU. It is the first case to be described in the literature of the comorbidity of PKU and Hirschsprung disease.

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“…Normal development and migration of the neural crest-derived intestinal ganglion cells involves genes in three different signaling pathways [12][13][14][15] : (i) the RET receptor tyrosine kinase pathway with genes encoding the RET receptor and its ligand, the glial cell line-derived neurotrophic factor (GDNF); the endothelin type B receptor pathway with the EDNR receptor and its ligand, endothelin-3 (EDN3); and (iii) SOX10-mediated transcription [6][7][8] . All told, mutations in eight partially-interdependent genes are associated with Hirschsprung disease (see table).…”

Section: Genetic Analysismentioning

confidence: 99%

Dissecting Hirschsprung disease

Passarge

2002

Nat Genet

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A gene for Hirschsprung disease maps to the proximal long arm of chromosome 10

Cited by 183 publications

References 36 publications

Low RET mutation frequency and polymorphism analysis of the RET and EDNRB genes in patients with Hirschsprung disease in Taiwan

Low RET mutation frequency and polymorphism analysis of the RET and EDNRB genes in patients with Hirschsprung disease in Taiwan

Phenylketonuria and Hirschsprung Disease—A Report of an Unusual Neonatal Presentation

Dissecting Hirschsprung disease

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