PMID- 10521296
OWN - NLM
STAT- MEDLINE
DCOM- 19991210
LR  - 20220310
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 5
DP  - 1999 Nov
TI  - The origins of hypertrophic cardiomyopathy-causing mutations in two South African
      subpopulations: a unique profile of both independent and founder events.
PG  - 1308-20
AB  - Hypertrophic cardiomyopathy (HCM) is an autosomal dominantly inherited disease of
      the cardiac sarcomere, caused by numerous mutations in genes encoding protein
      components of this structure. Mutation carriers are at risk of sudden cardiac
      death, mostly as adolescents or young adults. The reproductive disadvantage
      incurred may explain both the global occurrence of diverse independent
      HCM-associated mutations and the rare reports of founder effects within
      populations. We have investigated whether this holds true for two South African
      subpopulations, one of mixed ancestry and one of northern-European descent.
      Previously, we had detected three novel mutations-Ala797Thr in the beta-myosin
      heavy-chain gene (betaMHC), Arg92Trp in the cardiac troponin T gene (cTnT), and
      Arg645His in the myosin-binding protein C gene (MyBPC)-and two documented betaMHC
      mutations (Arg403Trp and Arg249Gln). Here we report three additional novel
      mutations-Gln499Lys in betaMHC and Val896Met and Deltac756 in MyBPC-and the
      documented betaMHC Arg719Gln mutation. Seven of the nine HCM-causing mutations
      arose independently; no conclusions can be drawn for the remaining two. However, 
      the betaMHC Arg403Trp and Ala797Thr and cTnT Arg92Trp mutations were detected in 
      another one, eight, and four probands, respectively, and haplotype analysis in
      families carrying these recurring mutations inferred their origin from three
      common ancestors. The milder phenotype of the betaMHC mutations may account for
      the presence of these founder effects, whereas population dynamics alone may have
      overridden the reproductive disadvantage incurred by the more lethal, cTnT
      Arg92Trp mutation.
FAU - Moolman-Smook, J C
AU  - Moolman-Smook JC
AD  - US/MRC Centre for Molecular and Cellular Biology, Department of Medical
      Biochemistry, University of Stellenbosch Medical School, Tygerberg, South Africa.
FAU - De Lange, W J
AU  - De Lange WJ
FAU - Bruwer, E C
AU  - Bruwer EC
FAU - Brink, P A
AU  - Brink PA
FAU - Corfield, V A
AU  - Corfield VA
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 (Carrier Proteins)
RN  - 0 (Troponin T)
RN  - 0 (myosin-binding protein C)
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
SB  - IM
MH  - Cardiomyopathy, Hypertrophic/ethnology/*genetics
MH  - Carrier Proteins/genetics
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 14
MH  - Female
MH  - *Founder Effect
MH  - Genotype
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - *Mutation
MH  - Myosin Heavy Chains/genetics
MH  - Pedigree
MH  - South Africa
MH  - Troponin T/genetics
PMC - PMC1288283
EDAT- 1999/10/16 09:00
MHDA- 2000/03/21 09:00
CRDT- 1999/10/16 09:00
PHST- 1999/10/16 09:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/10/16 09:00 [entrez]
AID - S0002-9297(07)62137-5 [pii]
AID - 10.1086/302623 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Nov;65(5):1308-20. doi: 10.1086/302623.