Deletion of PTEN and BMPR1A on Chromosome 10q23 Is Not Always Associated with Juvenile Polyposis of Infancy

Salviati, Leonardo; Patricelli, M.G.; Guariso, Graziella; Sturniolo, Giacomo Carlo; Alaggio, Rita; Bernardi, F; Zuffardi, Orsetta; Tenconi, Romano

doi:10.1086/507151

Cited by 40 publications

(46 citation statements)

References 12 publications

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“…Also in these cases, the coexistence of BRCA1/BRCA2 mutations in MEN1-mutated patients did not lead to a more severe clinical phenotype as instead observed in some oligogenic disorders such as in Kallmann syndrome (involving FGFR1 and NELF) or normosmic idiopathic hypogonadotropic hypogonadism (involving FGFR1 and GNRHR) (34). On the other hand, a high phenotypic variability could be observed also in patients with multiple mutations affecting the same tumor suppressor genes: simultaneous deletion of BMPR1a and PTEN may be associated with severe polyposis in some patients (35), but not in others (36).…”

Section: Discussionmentioning

confidence: 83%

Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia

Occhi¹,

Trivellin²,

Ceccato³

et al. 2010

European Journal of Endocrinology

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Background: Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene and the p27 KIP1 encoding gene CDKN1B have been associated with two well-defined hereditary conditions, familial isolated pituitary adenoma (FIPA) and multiple endocrine neoplasia type 4 (MEN4). Somatotropinomas are present in most AIP mutated FIPA kindreds, as well as in two-thirds of MEN4 patients who carry pituitary tumors. Methods: Germline DNA samples of 131 Italian sporadic acromegalic patients including 38 individuals with multiple tumors, and of six FIPA families (four homogeneous for prolactinomas and two heterogeneous with prolactin/nonfunctioning pituitary adenomas) were collected in a multicentric collaborative study. The prevalence of AIP and CDKN1B gene point mutations and copy number variations were evaluated. Results: Two novel (IVS3C1GOA and c.871GOA) and one previously described (c.911GOA) AIP mutations were detected in four apparently sporadic cases (3.1%) with relatively high age at diagnosis (49G18, range 30-67). No mutations/rearrangements were detected in FIPA families. The highly conserved c.871GOA substitution was detected in a patient who also carried a MEN1 mutation suggesting that she is a double heterozygote. The possible pathogenic effect on AIP splicing of the silent substitution c.144GOA found in another patient was ruled out using a minigene-based approach. CDKN1B mutations/rearrangements were neither identified in patients with multiple neoplasia nor in FIPA families. Conclusion: AIP is mutated in about 3% of apparently sporadic acromegalic patients. The relatively high age at diagnosis, as well as its sporadic presentation, suggests that these patients are carriers of mutations with reduced pathogenicity. p27 KIP1 is unlikely to represent the common unifying nonendocrine etiology for acromegaly and cancer.

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Section: Discussionmentioning

confidence: 83%

Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia

Occhi¹,

Trivellin²,

Ceccato³

et al. 2010

European Journal of Endocrinology

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“…BMPR1A is deleted in patients 3 and 4 and in all individuals who have been reported with overlapping deletions and cardiac septal defects. [41][42][43][44][45] Of these deletions, at least one did not include the GRID1 gene. 42 Cardiac-specific deletion of BMPR1A disrupts cardiac morphogenesis in mice, showing ventricular septum, trabeculae, compact myocardium and endocardial cushion defects.…”

Section: Discussionmentioning

confidence: 99%

The phenotype of recurrent 10q22q23 deletions and duplications

et al. 2011

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The genomic architecture of the 10q22q23 region is characterised by two low-copy repeats (LCRs3 and 4), and deletions in this region appear to be rare. We report the clinical and molecular characterisation of eight novel deletions and six duplications within the 10q22.3q23.3 region. Five deletions and three duplications occur between LCRs3 and 4, whereas three deletions and three duplications have unique breakpoints. Most of the individuals with the LCR3-4 deletion had developmental delay, mainly affecting speech. In addition, macrocephaly, mild facial dysmorphisms, cerebellar anomalies, cardiac defects and congenital breast aplasia were observed. For congenital breast aplasia, the NRG3 gene, known to be involved in early mammary gland development in mice, is a putative candidate gene. For cardiac defects, BMPR1A and GRID1 are putative candidate genes because of their association with cardiac structure and function. Duplications between LCRs3 and 4 are associated with variable phenotypic penetrance. Probands had speech and/or motor delays and dysmorphisms including a broad forehead, deep-set eyes, upslanting palpebral fissures, a smooth philtrum and a thin upper lip. In conclusion, duplications between LCRs3 and 4 on 10q22.3q23.2 may lead to a distinct facial appearance and delays in speech and motor development. However, the phenotypic spectrum is broad, and duplications have also been found in healthy family members of a proband. Reciprocal deletions lead to speech and language delay, mild facial dysmorphisms and, in some individuals, to cerebellar, breast developmental and cardiac defects.

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“…A less severe phenotype with childhood-onset and milder clinical course or early onset colorectal cancer in a young adult has been reported [2,7,8]. Dahdaleh et al concluded that, while the range of phenotypes is variable, JPI requires the loss of both BMPR1A and PTEN [5].…”

Section: Discussionmentioning

confidence: 99%

Juvenile polyposis of infancy in a child with deletion of BMPR1A and PTEN genes: Surgical approach

Oliveira

Cunha

Almeida

et al. 2013

Journal of Pediatric Surgery

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Juvenile polyposis of infancy is the most severe and life-threatening form of juvenile polyposis. This disease typically presents in the first two years of life with gastrointestinal bleeding, diarrhea, inanition, and exudative enteropathy. In very few reports concerning this entity, a large deletion in the long arm of chromosome 10 (10q23), encompassing the PTEN and BMPR1A genes, was found. The authors report a case of delayed diagnosis of juvenile polyposis of infancy at 6 years of age. A 3.34 Mb long de novo deletion was identified at 10q23.1q23.31, encompassing the PTEN and BMPR1A genes. The disease course was severe with diarrhea, abdominal pain, inanition, refractory anemia, rectal bleeding, hypoalbuminemia, and exudative enteropathy. A sub-total colectomy, combined with intraoperative endoscopic removal of ileal and rectal stump polyps, was required for palliative disease control.

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Deletion of PTEN and BMPR1A on Chromosome 10q23 Is Not Always Associated with Juvenile Polyposis of Infancy

Cited by 40 publications

References 12 publications

Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia

Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia

The phenotype of recurrent 10q22q23 deletions and duplications

Juvenile polyposis of infancy in a child with deletion of BMPR1A and PTEN genes: Surgical approach

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