PMID- 10690880
OWN - NLM
STAT- MEDLINE
DCOM- 20000309
LR  - 20101118
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 85
IP  - 2
DP  - 2000 Feb
TI  - Isolated familial somatotropinomas: establishment of linkage to chromosome 
      11q13.1-11q13.3 and evidence for a potential second locus at chromosome 2p16-12.
PG  - 707-14
AB  - 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.
FAU - Gadelha, M R
AU  - Gadelha MR
AD  - Department of Medicine, University of Illinois at Chicago, 60612, USA.
FAU - Une, K N
AU  - Une KN
FAU - Rohde, K
AU  - Rohde K
FAU - Vaisman, M
AU  - Vaisman M
FAU - Kineman, R D
AU  - Kineman RD
FAU - Frohman, L A
AU  - Frohman LA
LA  - eng
GR  - DK-30667/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
SB  - IM
CIN - J Clin Endocrinol Metab. 2000 Dec;85(12):4920-1. PMID: 11134164
MH  - Acromegaly/*genetics
MH  - Adolescent
MH  - Adult
MH  - *Chromosome Mapping
MH  - Chromosomes, Human, Pair 11/*genetics
MH  - Chromosomes, Human, Pair 17/genetics
MH  - Chromosomes, Human, Pair 2/*genetics
MH  - Female
MH  - *Genetic Linkage
MH  - Gigantism/*genetics
MH  - Haplotypes
MH  - Humans
MH  - Lod Score
MH  - Male
MH  - Pedigree
EDAT- 2000/02/26 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/02/26 09:00
PHST- 2000/02/26 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/02/26 09:00 [entrez]
AID - 10.1210/jcem.85.2.6386 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2000 Feb;85(2):707-14. doi: 10.1210/jcem.85.2.6386.