The genetics of infantile hypertrophic pyloric stenosis: A reanalysis
To determine whether the existing family data for infantile hypertrophic pyloric stenosis (IHPS) are sufficient for the purposes of establishing the mode of inheritance of this condition.
Reanalysis of the familial aggregation patterns exhibited by IHPS, using data from several published family studies.
Due to several limitations of the available family data for IHPS, the results of this analysis should be interpreted cautiously. Within the context of these limitations, the familial recurrence pattern among monozygotic cotwins and more remote relatives of IHPS probands was found to be inconsistent with generalized single major locus inheritance. The familial recurrence pattern of IHPS is, however, compatible with multifactorial threshold inheritance or the effects of multiple interacting loci. Under a model of multiple interacting loci, no single locus can account for more than a fivefold increase in the risk to first-degree relatives of IHPS probands. In contrast to several earlier reports, this analysis does not support the existence of a maternal factor that contributes to the risk of IHPS in the offspring of affected females.
Available from: Yuqiang Nie
- "IHPS is the most common gastrointestinal disease in the first few weeks of life. The male-to-female ratio is about 4∶1, ranging from 2.5∶1 to 5.5∶1 , , , , .It is demonstrated that there were 271 boys, male prevalence 271∶45 in our study. "
[Show abstract] [Hide abstract]
ABSTRACT: To investigate clinical features of infantile hypertrophic pyloric stenosis (IHPS) in Chinese Han population.
Three hundred and sixteen hospitalized patients with IHPS from January 1998 to February 2010 were retrospectively reviewed, and data including patient's sex, onset age, other coexisting congenital defects, pyloric circular muscle thickness evaluated by ultrasonograph, serum electrolytes concentration, and results of arterial blood gas analysis on admission were collected. The patients were divided into two groups: the duration between first onset and admission less than or equal to 10 days (early onset group), and more than 10 days (late onset group). The results of arterial blood gas and serum electrolyte concentration were compared between the two groups.
There were 271 males and 45 females in 316 patients; the onset age ranged between 1 and 351 (26.5±26.6) days. The birth weight ranged between 1.6 and 4.5 (3.23±0.44) kilograms; coexisting congenital defects were found in 65 cases (20.6%). Pyloric circular muscle thickness was 4-8 (5.4±1.0) millimetres (mm). For the early onset group, the rates of hypokalemia, hypochloraemia and hypercapnia were significantly lower than those in the late onset group (18.67% VS 50%, P<0.0001; 46.03% VS 71.01%, P = 0.003; 56.58% VS 83.44%, P = 2.17×10(-5); respectively).
The symptom duration in Chinese Han population was longer than that in other populations. And as the prolongation of symptom duration, the incidence of acid-base imbalance increased significantly. Infants with persistent vomiting at the age of 3∼5 weeks after birth should be considered IHPS, and go to hospital as soon as possible in order to reduce the incidence of hypokalemia, hypochloraemia and hypercapnia, and avoid deterioration.
Available from: Kate V Everett
- "The previous identiWcation of TRPC5 and TRPC6 as the best functional candidates in the chromosome X and 11 loci lent support to the argument for TRPC1 as a functional candidate within the chromosome 3q21–q24 locus. The recurrence pattern of IHPS is compatible with a multifactorial threshold model of inheritance or the eVects of multiple loci, with no single locus accounting for more than a Wvefold increase in risk to Wrst degree relatives (Mitchell and Risch 1993). Therefore, we would expect there to be only a few relatively common variants within each susceptibility gene which account for the linkage signals seen and that tagSNP association analysis and resequencing would detect these variants. "
[Show abstract] [Hide abstract]
ABSTRACT: Infantile hypertrophic pyloric stenosis (IHPS) is the most common inherited form of gastrointestinal obstruction in infancy
with a striking male preponderance. Infants present with vomiting due to gastric outlet obstruction caused by hypertrophy
of the smooth muscle of the pylorus. Two loci specific to extended pedigrees displaying autosomal dominant inheritance have
been identified. A genome scan identified loci on chromosomes 11q14–q22 and Xq23–q24 which are predicted to be responsible
for a subset of smaller families with IHPS demonstrating non-Mendelian inheritance. The two linked chromosomal regions both
harbour functional candidate genes which are members of the canonical transient receptor potential (TRPC) family of ion channels.
Both TRPC5 (Xq23–q24) and TRPC6 (11q14–q22) have a potential role in smooth muscle control and hypertrophy. Here, we report suggestive evidence for a third
locus on chromosome 3q12–q25 (Z
max=2.7, p<0.004), a region which harbours a third TRPC gene, TRPC1. Fine mapping of all three genes using a tagSNP approach and re-sequencing identified a SNP in the promoter region of TRPC6 and a missense variant in exon 4 of TRPC6 which may be putative causal variants.
Available from: Weiming xu
- "This is supported by subsequent studies (Chakraborty 1986; Mitchell and Risch 1993). A recent reanalysis of the genetics of PS concluded that PS is determined by either a multifactorial inheritance or multiple interacting loci with no single gene accounting for more than a fivefold increase in the risk to first-degree relatives and that, at most, two or three loci of moderate effect are involved in the etiology of PS (Mitchell and Risch 1993). Recent evidence has implicated the enzyme neuronal nitric oxide synthase (nNOS) in the etiology of PS, rendering its gene (NOS1) a candidate gene for the condition . "
[Show abstract] [Hide abstract]
ABSTRACT: The etiological role of the gene for neuronal nitric oxide synthase (NOS1) in infantile pyloric stenosis (PS) was investigated by analysis of two intragenic polymorphisms (NOS1a and NOS1b) in 27 families. There was significant overall transmission disequilibrium between PS and NOS1a (P = .006). Consideration of each allele independently revealed a highly significant tendency for allele 7 (210 bp) to be preferentially transmitted to the affected offspring (P = .0006). These observations suggest that NOS1 is a susceptibility locus for PS.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.