林興中 醫師 於 1980-01-01 00:00:00 回覆

肢端肥大症在文獻上是有報告可出現家族遺傳的病例，其中有部份是\r
1.「第一型多發性內分泌新生症（Multiple Endocrine Neoplasia,MEN-1）」病例，即家族中的人不止得到腦下垂體腫瘤導致之肢端肥大症、尚可能患有副甲狀腺功能亢進、及胰島細胞腫瘤（最常見者為gastrinoma），主要病因為MEN-1基因突變或缺陷造成。\r
以下提供一份文獻給妳參考，全文請自行到圖書館或向國外申購。\r
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Pituitary 1999 May;1(3-4):273-7 \r
Familial acromegaly: case report and review of the literature.\r
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Verloes A, Stevenaert A, Teh BT, Petrossians P, Beckers A.\r
Wallonia Centre for human Genetics, Liege University, Belgium.\r
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Familial acromegaly is an exceptional clinical entity when not associated with features of multiple endocrine neoplasia type 1 (MEN1). We report here 3 pedigrees in each of which 2 patients have been shown to develop acromegaly. In 4 patients, clinical follow-up, and biological screening allowed to confidently exclude MEN1. Absence of mutation in the MEN1 gene after direct DNA analysis in 2 pedigrees reinforces the conviction that the families do not have MEN1. In families 1 and 2, diagnosis was made at a very early age and voluminous adenomas with suprasellar expansion were already present at the time of diagnosis. We review the 20 previous reports of familial acromegaly, some of them questionable. Our 3 families, combined with some other published pedigrees, allow the delineation of a familial form of acromegaly, distinct from MEN1. Dominant inheritance with reduced, age-dependant penetrance is the most parsimonious model to explain the recurrences. Gs protein pathway could be the site of action of the gene responsible of familial acromegaly, but no data have been published to sustain or reject this hypothesis.\r
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2.也有部份是單純性的腦下垂體腫瘤導致之肢端肥大症（Isolated familial somatotropinomas），有報告是第2對或第11對染色體突變造成。\r
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以下提供一份文獻給妳參考，全文請自行到圖書館或向國外申購。\r
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J Clin Endocrinol Metab 2000 Feb;85(2):707-14\r
Isolated familial somatotropinomas: establishment of linkage to chromosome 11q13.1-11q13.3 and evidence for a potential second locus at chromosome 2p16-12.\r
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Gadelha MR, Une KN, Rohde K, Vaisman M, Kineman RD, Frohman LA.\r
Department of Medicine, University of Illinois at Chicago, 60612, USA.\r
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The majority of somatotropinomas are sporadic, although a small number occur with a familial aggregation, either as a component of an endocrine neoplasia complex that includes multiple endocrine neoplasia type 1 (MEN-1) and Carney complex (CNC) or as isolated familial somatotropinomas (IFS). IFS is defined as the occurrence of at least two cases of acromegaly or gigantism in a family that does not exhibit MEN-1 or CNC. This rare disease is associated with loss of heterozygosity (LOH) on chromosome 11q13, the locus of the MEN-1 gene, although the MEN-1 sequence and expression appear normal. These data suggest the presence of another tumor suppressor gene located at 11q13 that is important in the control of somatotrope proliferation. To establish linkage of IFS to 11q13 and to define the candidate interval of the IFS gene, we performed haplotype and allelotype analyses on two families with IFS. Collectively, allelic retention in one tumor and a recombinant haplotype in an affected individual mapped the tumor suppressor gene involved in the pathogenesis of IFS to a region of 8.6 cM between polymorphic microsatellite markers D11S1335 and INT-2 located at chromosome 11q13.1-13.3. Maximum two-point LOD scores for five markers within this region were 3.0 or more at theta = 0.0. As somatotropinomas are the predominant pituitary tumor subtype associated with CNC and arise before 30 yr of age, which is strikingly similar to the age at diagnosis for IFS, we explored the possibility that the putative CNC genes might also contribute to the pathogenesis of IFS. Although the genetic defect responsible for the complex is unknown, CNC has been mapped by linkage analysis to chromosomes 2p15-16 and 17q23-24 in different kindreds. Two-point LOD scores less than -2.0 were obtained using marker D17S949 from chromosome 17q23-24, excluding linkage. However, LOD scores of 2.5 were obtained for markers within 2p16-12; therefore, linkage of IFS to chromosome 2p cannot be excluded. This report establishes linkage of the tumor suppressor gene involved in the pathogenesis of IFS to chromosome 11q13.1-13.3 and identifies a potential second locus at chromosome 2p16-12.\r


林興中醫師　2002/06/07/14:52:59