A meiotic recombination in a new isolated familial somatotropinoma kindred

Abstract

We report here the genetic findings of a new isolated familial somatotropinoma (IFS) kindred in which the mother (subject I:2) and one daughter (subject II:2) are affected; their ages at diagnosis were 25 and 14 years respectively. Additionally, patient I:2 developed virilization due to an androgen-secreting adrenocortical mass, presenting clinical and molecular features of sporadic adrenal carcinoma. To genotype this family and to narrow down the candidate interval of the putative IFS gene at 11q13, we performed haplotyping on the DNA from all five members of the family and allelotyping of one available somatotropinoma using polymorphic microsatellite markers from chromosome region 11q12.1 -11q13.5. Results indicated that the disease haplotype, between markers D11S956 and D11S527, was transmitted from subject I:2 only to subject II:2. A meiotic recombination event was detected in the fraternal twin sister of II:2 (subject II:1), but her disease status is unknown. Since she is only 18 years old this genetic event cannot yet narrow down the area involved in the pathogenesis of IFS. Allelotyping of the somatotropinoma from II:2 revealed loss of the chromosome carrying the wild-type copy of the putative IFS gene inherited from her father. These results support the involvement of a tumor suppressor gene at 11q13.1 -q13.3 in the pathogenesis of IFS.European Journal of Endocrinology 150 643-648

The clinical, pathological, and genetic features of familial isolated pituitary adenomas

“…No relevant family history of MEN1-like features was seen and limited family screening (one brother) was negative. Despite the MEN1-like features of the patients described, studies from Ozawa and colleagues at the NIH and from (24). Despite the advent of mutations in AIP as potential causative features in IFS, the genetic pathophysiology of IFS remains to be fully described as we have found that in 50% of IFS families, no AIP mutations exist (25).…”

Growth hormone- secreting pituitary adenomas: from molecular basis to treatment options in acromegaly

“…47 In 2004, Luccio et al narrowed the area involved in the pathogenesis of IFS. 48 In 2005, Soares et al further narrowed the area involved in the IFS. 49 In 2006, Vierimaa et al identified germline mutations (nonsense mutation Q14X in exon 1, splice site mutation IVS3-1G>A in exon 4 and a nonsense mutation R304X in exon 6) in the AIP gene in individuals with PAP.…”

Growth Hormone-Secreting Tumors: Genetic Aspects and Data from Animal Models

“…Apart from the linkage of IFS to 11q13, the possibility for a linkage to 2p16 has also been raised, although data are still inconclusive [71,72,73]. Additional analysis of IFS families and tumor deletion mapping in sporadic somatotropinomas allowed the positioning of the IFS locus to be narrowed down to a 3.9-Mb area between markers D11D4908 and INT2 at 11q13 [74]. Furthermore, recent analysis narrowed the IFS locus down to a 2.21-Mb area between markers D11S4155 and D11S4136 at 11q13 (fig.…”