A case of Hirschsprung disease with a chromosome 13 microdeletion, del(13)(q32.3q33.2): potential mapping of one disease locus

Bottani, Armand; Xie, Yang; Binkert, F.; Schinzel, Albert

doi:10.1007/bf00201741

Cited by 46 publications

(23 citation statements)

References 21 publications

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“…A more recent observation of a HSCR patient (Bottani et al, 1991) showing an interstitial deletion in 13q32.3->q33.2 suggested this terminal region of chromosome 13 as a possible candidate location for the disease gene.…”

Section: Discussionmentioning

confidence: 99%

Deleted and normal chromosome 10 homologs from a patient with Hirschsprung disease isolated in two cell hybrids through enrichment by immunomagnetic selection

Puliti

Covone

Bicocchi

et al. 1993

Cytogenet Genome Res

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A cytogenetically detectable deletion, del(10) (q11.2→q21.2), was observed in a patient with total colonic aganglionosis with small bowel involvement (TCSA), a variant of Hirschsprung disease (HSCR). A similar deletion is present in another TCSA patient (S.M. Huson, personal communication). To reveal cytogenetically undetectable deletions of chromosome 10 in further patients, we developed a strategy for mapping chromosome 10 DNA markers with respect to the observed deletions. To this end, the two chromosome 10 homologs (deleted and normal) were segregated in two distinct somatic cell hybrids obtained after fusion of the patient’s fibroblasts with a Chinese hamster ovary cell line (YH21). Hybrid cells containing chromosome 10 were selected for the expression of the gene coding for the β subunit of the fibronectin receptor (FNRB), which maps to lOpl 1.2, using a monoclonal antibody against FNRB. Hybrid 185.0 contains the deleted chromosome, whereas hybrid 179.Q contains the nondeleted one. Southern blot and PCR analysis of DNA from these two hybrids mapped the markers RBP3H4, RET, D10S15, D10S5, D10S22, and D10S88 inside the deletion and D10S170, CDC2, EGR2, and D10S19 outside the deletion. MEN2A and MEN2B have recently been mapped within the centromeric region closely linked to RBP3 and D10S15 (which are located inside the deletion) and cosegregate with HSCR in at least two different pedigrees. Since HSCR, MEN2A, and MEN2B represent defects of neural crest cell development, we hypothesize that they originate from mutations in different genes clustered in the centromeric region of 1 Oq.

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Section: Discussionmentioning

confidence: 99%

Deleted and normal chromosome 10 homologs from a patient with Hirschsprung disease isolated in two cell hybrids through enrichment by immunomagnetic selection

Puliti

Covone

Bicocchi

et al. 1993

Cytogenet Genome Res

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“…For example, the disease has been associated with a deletion of band 22p22 and a reciprocal translocation (3;7)(p21;q22),25 a deletion in chromosome 13 (q32.3q33.2),26 and others 126 However, the types of gene defects present in a major proportion of Hirschsprung’s disease families are mutations in chromosome 10q11.2,27 28 which have now been found to be associated with the proto-oncogene, ret 45In addition, several other families with Hirschsprung’s disease have an associated mutation located at chromosome 13q22 which is in the endothelin receptor-B (ENDR-B) gene 6…”

Section: Genetics Of Hirschsprung’s Diseasementioning

confidence: 99%

Hirschsprung’s disease: genetic mutations in mice and men

Robertson

Mason

Hall

1997

Gut

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Hirschsprung’s disease is a neuronal dysplasia of the hindgut, characterised by a loss of neurones, which affects about 1 in 5000 live births.1 Genetic factors have been implicated in the aetiology of this disease in about 20% of cases and a dominant pattern of inheritance has been revealed in several families.2 3The pathogenesis of the aganglionosis is often attributed to a failure of migration of neural crest cells, although this has not been proven.Recently, mutations in a developmentally regulated receptor tyrosine kinase gene, ret, and mutations in the endothelin receptor-B gene (ENDR-B) have both been linked to familial Hirschsprung’s disease in humans.4-6 Moreover, certain mutant mouse strains—namely piebald lethal and lethal spotted—exhibit striking similarities to the human condition. The mutation which gives rise to piebald lethal has now been found to be in the ENDR-B gene,7 and the mutation associated with lethal spotted occurs in the gene for endothelin-3 (ET-3), a ligand for ENDR-B.8 Two transgenic mouse lines have been developed which also reflect the human disease: ret-k−, which has aloss of function mutation of the retgene,9 and ENDR-B null.10 In addition, the introduction of a Lac-Z reporter gene into neural crest cells of aganglionic mice has made it possible to study directly the fate of enteric neuroblasts which are affected by “Hirschsprung’s-like” mutations.11 Here, we review the possible roles of RET and endothelin in the normal development of the enteric nervous system, and the significance of their mutated forms in the pathogenesis of familial aganglionosis.This review focuses on recent advances in our understanding of the genetic basis of the lesions which have been implicated in congenital forms of Hirschsprung’s disease. Disruption of these genes in the mouse, either by transgenic “knockout” approaches or in mutant mouse lines, offers the prospect of greater understanding of both the cellular and developmental bases of the human disease.

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“…Depending upon the deleted segment, clinical manifestations have been variable and have included retinoblastoma, mental and growth retardation, craniofacial abnormalities, brain, gastrointestinal, renal and heart malformation, anal atresia, limb and digit malformations. (Brown et al, 1993;Walsh et al, 2001;Carmichael et al, 1977;Cuschieri et al, 1977;Telfer et al, 1980;Bottani et al, 1991). Several patients have been described with a mosaic pattern of 13q deletion showing both a normal and a deleted 13q in each cell line investigated (Niikawa et al, 1980;Dudin et al, 1984;Ribeiro et al, 1988;Bunin et al, 1989;Bamforth and Lin, 1997;Gentile et al, 1999;Lorentz et al, 2002;Widschwendter et al, 2002;Van Esch et al, 2005).…”

Section: Discussionmentioning

confidence: 95%

Mosaic 13q13.2-ter deletion restricted to tissues of ectodermal and mesodermal origins

Melis

Sperandeo²,

Perone³

et al. 2006

Clinical Dysmorphology

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The '13q-' syndrome shows widely variable manifestations. Investigation of the involvement of different tissues has never been reported in patients with 13q- syndrome previously. We describe a patient with mosaicism for del(13q) and clinical features of 13q- syndrome. The mother of the patient was professionally exposed to aniline colorants and glue components during the whole pregnancy. The patient had dysmorphic features, skeletal anomalies and brain malformations with agenesis of the corpus callosum, vermian hypoplasia and IVth ventricular system abnormalities. Eye examination revealed chorioretinal coloboma and irregular dispersion of retinal pigment in the right eye. The karyotype analyses and the molecular studies performed on peripheral lymphocytes, oral swab and cells of urinary tract were normal whereas a deletion of the long arm of chromosome 13 (13q13.2) was found in skin fibroblasts and in hair cells. We hypothesized that the 13q deletion arose during the third week after conception possibly due to a teratogenic effect and that tissue of mesodermal and ectodermal origin are involved. We suggest analysing a fibroblast karyotype when a diagnosis of 13q- syndrome is suspected on clinical ground. The role of teratogens in causing this type of mosaic chromosome abnormality also warrants further investigation.

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A case of Hirschsprung disease with a chromosome 13 microdeletion, del(13)(q32.3q33.2): potential mapping of one disease locus

Cited by 46 publications

References 21 publications

Deleted and normal chromosome 10 homologs from a patient with Hirschsprung disease isolated in two cell hybrids through enrichment by immunomagnetic selection

Deleted and normal chromosome 10 homologs from a patient with Hirschsprung disease isolated in two cell hybrids through enrichment by immunomagnetic selection

Hirschsprung’s disease: genetic mutations in mice and men

Mosaic 13q13.2-ter deletion restricted to tissues of ectodermal and mesodermal origins

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