PMID- 19141585
OWN - NLM
STAT- MEDLINE
DCOM- 20090528
LR  - 20230411
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 94
IP  - 5
DP  - 2009 May
TI  - Rare germline mutations in cyclin-dependent kinase inhibitor genes in multiple 
      endocrine neoplasia type 1 and related states.
PG  - 1826-34
LID - 10.1210/jc.2008-2083 [doi]
AB  - CONTEXT: Germline mutation in the MEN1 gene is the usual cause of multiple 
      endocrine neoplasia type 1 (MEN1). However, the prevalence of identifiable 
      germline MEN1 mutations in familial MEN1 cases is only 70%. Some cases may have a 
      germline mutation in another gene such as the p27 cyclin-dependent kinase 
      inhibitor (CDKI). OBJECTIVE: The aim of the study was to investigate cases of 
      MEN1 or related states for germline mutations in all CDKI genes. METHODS: A total 
      of 196 consecutive index cases were selected with clear or suspected MEN1 and no 
      identifiable germline MEN1 mutation. Every case was analyzed for germline 
      mutation in each of the seven CDKI genes. RESULTS: We identified benign 
      polymorphisms of the CDKI genes and also 15 other initially unclassified sequence 
      variants. After detailed gene/protein analysis, seven of these 15 variants were 
      classified as probably pathological mutations. Three of these seven were probable 
      mutations of p27. The remaining four were probable pathological mutations in 
      three of the other CDKI genes, thereby implicating these three genes in the 
      germline of human tumors. The identification rates for probably pathological 
      mutations among the 196 index cases were similarly low for each of four CDKI 
      genes: p15 (1%), p18 (0.5%), p21 (0.5%), and p27 (1.5%). No characteristic 
      clinical subtype related to MEN1 was identified among the seven index cases and 
      their families. CONCLUSION: Rare germline mutation in any among four (p15, p18, 
      p21, and p27) of the seven CDKIs is a probable cause of MEN1 or of some related 
      states.
FAU - Agarwal, Sunita K
AU  - Agarwal SK
AD  - National Institute of Diabetes and Digestive and Kidney Diseases, National 
      Institutes of Health, Bethesda, Maryland 20892-1802, USA. SunitaA@mail.nih.gov
FAU - Mateo, Carmen M
AU  - Mateo CM
FAU - Marx, Stephen J
AU  - Marx SJ
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20090113
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Isoenzymes)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 63231-63-0 (RNA)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
EIN - J Clin Endocrinol Metab. 2009 Jul;94(7):2674
CIN - J Clin Endocrinol Metab. 2009 May;94(5):1518-20. PMID: 19420274
MH  - Cyclin-Dependent Kinase Inhibitor p27/biosynthesis/genetics
MH  - Cyclin-Dependent Kinases/*genetics
MH  - DNA/genetics/isolation & purification
MH  - Germ-Line Mutation/genetics/*physiology
MH  - Humans
MH  - Isoenzymes/genetics
MH  - Multiple Endocrine Neoplasia Type 1/*enzymology/*genetics
MH  - Pedigree
MH  - RNA/genetics/isolation & purification
PMC - PMC2684477
EDAT- 2009/01/15 09:00
MHDA- 2009/05/29 09:00
PMCR- 2010/05/01
CRDT- 2009/01/15 09:00
PHST- 2009/01/15 09:00 [entrez]
PHST- 2009/01/15 09:00 [pubmed]
PHST- 2009/05/29 09:00 [medline]
PHST- 2010/05/01 00:00 [pmc-release]
AID - jc.2008-2083 [pii]
AID - 6401 [pii]
AID - 10.1210/jc.2008-2083 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2009 May;94(5):1826-34. doi: 10.1210/jc.2008-2083. Epub 
      2009 Jan 13.