PMID- 9683585
OWN - NLM
STAT- MEDLINE
DCOM- 19981224
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 63
IP  - 2
DP  - 1998 Aug
TI  - Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 
      and related disorders.
PG  - 455-67
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome 
      predisposing to tumors of the parathyroid, endocrine pancreas, anterior 
      pituitary, adrenal glands, and diffuse neuroendocrine tissues. The MEN1 gene has 
      been assigned, by linkage analysis and loss of heterozygosity, to chromosome 
      11q13 and recently has been identified by positional cloning. In this study, a 
      total of 84 families and/or isolated patients with either MEN1 or MEN1-related 
      inherited endocrine tumors were screened for MEN1 germ-line mutations, by 
      heteroduplex and sequence analysis of the MEN1 gene-coding region and 
      untranslated exon 1. Germ-line MEN1 alterations were identified in 47/54 (87%) 
      MEN1 families, in 9/11 (82%) isolated MEN1 patients, and in only 6/19 (31.5%) 
      atypical MEN1-related inherited cases. We characterized 52 distinct mutations in 
      a total of 62 MEN1 germ-line alterations. Thirty-five of the 52 mutations were 
      frameshifts and nonsense mutations predicted to encode for a truncated MEN1 
      protein. We identified eight missense mutations and five in-frame deletions over 
      the entire coding sequence. Six mutations were observed more than once in 
      familial MEN1. Haplotype analysis in families with identical mutations indicate 
      that these occurrences reflected mainly independent mutational events. No MEN1 
      germ-line mutations were found in 7/54 (13%) MEN1 families, in 2/11 (18%) 
      isolated MEN1 cases, in 13/19 (68. 5%) MEN1-related cases, and in a kindred with 
      familial isolated hyperparathyroidism. Two hundred twenty gene carriers (167 
      affected and 53 unaffected) were identified. No evidence of genotype-phenotype 
      correlation was found. Age-related penetrance was estimated to be >95% at age >30 
      years. Our results add to the diversity of MEN1 germ-line mutations and provide 
      new tools in genetic screening of MEN1 and clinically related cases.
FAU - Giraud, S
AU  - Giraud S
AD  - Service de Genetique, Laboratoire de Genetique et Cancer, CNRS UMR 5641, Faculte 
      de Medecine Rockefeller, Lyon, France.
FAU - Zhang, C X
AU  - Zhang CX
FAU - Serova-Sinilnikova, O
AU  - Serova-Sinilnikova O
FAU - Wautot, V
AU  - Wautot V
FAU - Salandre, J
AU  - Salandre J
FAU - Buisson, N
AU  - Buisson N
FAU - Waterlot, C
AU  - Waterlot C
FAU - Bauters, C
AU  - Bauters C
FAU - Porchet, N
AU  - Porchet N
FAU - Aubert, J P
AU  - Aubert JP
FAU - Emy, P
AU  - Emy P
FAU - Cadiot, G
AU  - Cadiot G
FAU - Delemer, B
AU  - Delemer B
FAU - Chabre, O
AU  - Chabre O
FAU - Niccoli, P
AU  - Niccoli P
FAU - Leprat, F
AU  - Leprat F
FAU - Duron, F
AU  - Duron F
FAU - Emperauger, B
AU  - Emperauger B
FAU - Cougard, P
AU  - Cougard P
FAU - Goudet, P
AU  - Goudet P
FAU - Sarfati, E
AU  - Sarfati E
FAU - Riou, J P
AU  - Riou JP
FAU - Guichard, S
AU  - Guichard S
FAU - Rodier, M
AU  - Rodier M
FAU - Meyrier, A
AU  - Meyrier A
FAU - Caron, P
AU  - Caron P
FAU - Vantyghem, M C
AU  - Vantyghem MC
FAU - Assayag, M
AU  - Assayag M
FAU - Peix, J L
AU  - Peix JL
FAU - Pugeat, M
AU  - Pugeat M
FAU - Rohmer, V
AU  - Rohmer V
FAU - Vallotton, M
AU  - Vallotton M
FAU - Lenoir, G
AU  - Lenoir G
FAU - Gaudray, P
AU  - Gaudray P
FAU - Proye, C
AU  - Proye C
FAU - Conte-Devolx, B
AU  - Conte-Devolx B
FAU - Chanson, P
AU  - Chanson P
FAU - Shugart, Y Y
AU  - Shugart YY
FAU - Goldgar, D
AU  - Goldgar D
FAU - Murat, A
AU  - Murat A
FAU - Calender, A
AU  - Calender A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Amino Acid Substitution
MH  - Exons
MH  - Female
MH  - Genetic Carrier Screening
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Introns
MH  - Male
MH  - Multiple Endocrine Neoplasia/classification/*genetics
MH  - Multiple Endocrine Neoplasia Type 1/classification/*genetics
MH  - *Mutation
MH  - Mutation, Missense
MH  - Neoplasm Proteins/*genetics
MH  - Pedigree
MH  - Point Mutation
MH  - *Proto-Oncogene Proteins
MH  - Sequence Deletion
PMC - PMC1377295
EDAT- 1998/07/31 02:03
MHDA- 2000/03/21 09:00
PMCR- 1999/02/01
CRDT- 1998/07/31 02:03
PHST- 1998/07/31 02:03 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1998/07/31 02:03 [entrez]
PHST- 1999/02/01 00:00 [pmc-release]
AID - S0002-9297(07)61489-X [pii]
AID - 10.1086/301953 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1998 Aug;63(2):455-67. doi: 10.1086/301953.