PMID- 24074368
OWN - NLM
STAT- MEDLINE
DCOM- 20140422
LR  - 20230411
IS  - 1469-5073 (Electronic)
IS  - 0016-6723 (Linking)
VI  - 95
IP  - 4
DP  - 2013 Aug
TI  - Missense mutation in the MEN1 gene discovered through whole exome sequencing 
      co-segregates with familial hyperparathyroidism.
PG  - 114-20
LID - 10.1017/S0016672313000141 [doi]
AB  - Familial isolated hyperparathyroidism (FIHP) can be encountered in the context of 
      multiple endocrine neoplasia type 1 (MEN1), hyperparathyroidism and jaw tumour 
      syndrome (HPT-JT) and in familial hypocalciuric hypercalcaemia (FHH). In these 
      syndromes, germline mutations in the relevant genes (MEN1, HPRT2 and CaSR, 
      respectively) are detected. In some FIHP cases, the causative gene is still 
      elusive. The objective of this study is to define the genetic basis of FIHP in a 
      Georgian Jewish family with FIHP using whole exome capture and sequencing. DNA 
      extracted from two sibs and one offspring from a single family all affected with 
      multiglandular hyperparathyroidism was subjected to whole exome capturing and 
      sequencing using the Roche NimbleGen V2 chip and the Illumina HiSeq2000 
      sequencing platform. Genetic variants were detected and annotated using a 
      combination of the Genome Analysis Tool Kit and in-house scripts. Subsequent 
      confirmation of the mutations and co-segregation analyses were carried out by 
      Sanger sequencing in additional affected and unaffected family members. Whole 
      exome capture and sequencing revealed the collection of variations common to the 
      three-sequenced patients, including a very rare previously described missense 
      mutation (c.T1021C: p.W341R) in the MEN1 gene. The p.W341R mutation in the MEN1 
      gene showed complete co-segregation in the family. Whole exome capture and 
      sequencing led to the discovery of a missense mutation in the MEN1 gene and 
      ruling out of the additional candidates in a single experiment. The limited 
      expressivity of this mutation may imply a specific genotype-phenotype correlation 
      for this mutation.
FAU - Isakov, Ofer
AU  - Isakov O
AD  - Department of Cell and Developmental Biology, The Sackler School of Medicine, Tel 
      Aviv University, Tel-Aviv, Israel.
FAU - Rinella, Erica S
AU  - Rinella ES
FAU - Olchovsky, David
AU  - Olchovsky D
FAU - Shimon, Ilan
AU  - Shimon I
FAU - Ostrer, Harry
AU  - Ostrer H
FAU - Shomron, Noam
AU  - Shomron N
FAU - Friedman, Eitan
AU  - Friedman E
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - England
TA  - Genet Res (Camb)
JT  - Genetics research
JID - 101550220
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - Hyperparathyroidism 3
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Exome/genetics
MH  - Family
MH  - Female
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Hyperparathyroidism, Primary/*genetics
MH  - Male
MH  - Middle Aged
MH  - *Mutation, Missense
MH  - Pedigree
MH  - Proto-Oncogene Proteins/*genetics
MH  - Sequence Analysis, DNA
MH  - Young Adult
EDAT- 2013/10/01 06:00
MHDA- 2014/04/23 06:00
CRDT- 2013/10/01 06:00
PHST- 2013/10/01 06:00 [entrez]
PHST- 2013/10/01 06:00 [pubmed]
PHST- 2014/04/23 06:00 [medline]
AID - S0016672313000141 [pii]
AID - 10.1017/S0016672313000141 [doi]
PST - ppublish
SO  - Genet Res (Camb). 2013 Aug;95(4):114-20. doi: 10.1017/S0016672313000141.