Doktorsv÷rn Ý lŠknavÝsindum

Doktorsv÷rn Ý lŠknavÝsindum Ůri­judaginn 14. maÝ ver Berglind A­alsteinsdˇttir doktorsritger­ sÝna Ý lŠknavÝsindum vi­ LŠknadeild Hßskˇla ═slands.

Doktorsv÷rn Ý lŠknavÝsindum

Doktorsv÷rn Ý lŠknavÝsindum
Doktorsv÷rn Ý lŠknavÝsindum

Ůri­judaginn 14. maÝ ver Berglind A­alsteinsdˇttir doktorsritger­ sÝna Ý lŠknavÝsindum vi­ LŠknadeild Hßskˇla ═slands. Ritger­in ber heiti­: Arfger­ og svipger­ ofvaxtarhjartav÷­vakvilla ß ═slandi. Hypertrophic Cardiomyopathy in Iceland - A Nationwide Genotype - Phenotype Study.

AndmŠlendur eru dr. Perry M. Elliott, prˇfessor vi­ University College Ý London, og dr. Stellan M÷rner, dˇsent vi­ Hßskˇlann Ý Umeň.

Umsjˇnarkennari og lei­beinandi var dr. Gunnar ١r Gunnarsson, sÚrfrŠ­ingur Ý hjartalŠkningum og lyflŠkningum vi­ Sj˙krah˙si­ ß Akureyri og lektor vi­ LŠknadeild Hßskˇla ═slands. Me­lei­beinandi var Hilma Hˇlm, sÚrfrŠ­ingur hjß ═slenskri erf­agreiningu.

Auk ■eirra sßtu Ý doktorsnefnd ■au dr. DavÝ­ O. Arnar, gestaprˇfessor, Barry J. Maron, yfirlŠknir vi­ Tufts Medical Center Ý Boston, og dr. Jonathan G. Seidman, prˇfessor vi­ Harvard Medical School Ý Boston.

Dr. Ingibj÷rg Har­ardˇttir, prˇfessor og varaforseti LŠknadeildar Hßskˇla ═slands, stjˇrnar ath÷fninni sem fer fram Ý HßtÝ­asal Hßskˇla ═slands og hefst kl. 13.00.

┴grip af rannsˇkn
Ofvaxtarhjartav÷­vakvilli (OHK) er arfgengur hjartasj˙kdˇmur sem einkennist af ■ykknun hjartav÷­va. Sj˙kdˇmsmyndin er breytileg, margir eru einkennalausir en sj˙kdˇmurinn getur valdi­ hjartabilun, hjartslßttartruflunum og skyndidau­a.

Meginmarkmi­ rannsˇknarinnar var a­ kanna algengi, arfger­ og svipger­ OHK ß ═slandi. Leitast var vi­ a­ finna alla sj˙klinga sem greinst h÷f­u me­ OHK ß ═slandi ß tÝmabilinu 1997-2010 og ■eim bo­in ■ßtttaka Ý erf­arannsˇkn. ═ framhaldinu var ■eim sem greindust me­ sj˙kdˇmsvaldandi st÷kkbreytingu og nßnum Šttingjum ■eirra bo­in ■ßtttaka Ý frekari rannsˇkn. Alls greindust 180 sj˙klingar me­ OHK, ■ar af gengust 151 undir erf­arannsˇkn sem leiddi til greiningar ß sj˙kdˇmsvaldandi st÷kkbreytingu hjß 101 einstaklingi (67%). Megin■orri ■eirra h÷f­u s÷mu st÷kkbreytinguá Ý MYBPC3 geninu (c.927-2A>G). Fj÷lskylduskimun 225 fyrstu grß­u Šttingja leiddi til greiningar ß 108 arfberum st÷kkbreytingarinnar. Af ■eim var um ■a­ bil helmingur me­ merki um sj˙kdˇminn. Karlar sem bera st÷kkbreytinguna vir­ast vera lÝklegri en konur til a­ ■rˇa me­ sÚr sj˙kdˇminn ß yngri ßrum en ßhŠttan eykst me­ aldri hjß bß­um kynjum. Sameiginleg setr÷­ umhverfis st÷kkbreytinguna bendir til a­ ■essir einstaklingar hafi erft st÷kkbreytinguna frß sameiginlegum forf÷­ur frß 15. ÷ld. ┴Štla­ algengi st÷kkbreytingarinnar ß ═slandi er 0.36% og fj÷ldi arfbera ■vÝ um 1200 manns.

Rannsˇknin leiddi einnig Ý ljˇs a­ 5% sj˙klinga (8 einstaklingar) sem h÷f­u greinst me­ OHK reyndust hafa sjaldgŠfan efnaskiptasj˙kdˇm, svokalla­an Fabry sj˙kdˇm. Skortur ß ensÝminu α-galaktˇsÝdasa getur valdi­ fj÷llÝffŠrakerfasj˙kdˇmi sem getur me­al annars lagst ß hjarta, taugakerfi og nřru. Fj÷lskylduskimun leiddi til greiningar ß 33 einstaklingum til vi­bˇtar me­ Fabry sj˙kdˇm. Sj˙kdˇminn er hŠgt a­ me­h÷ndla me­ ensÝmuppbˇtarme­fer­ og ■vÝ er rÚtt greining mikilvŠg. Me­fer­in er einkum ßrangursrÝk hefjist h˙n snemma, ß­ur en lÝffŠraskemmdir hafa ßtt sÚr sta­.á áá

Abstract
Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous disorder with variable clinical expression. The primary aim of the study was to identify the prevalence, genetic causes and phenotypic spectrum of HCM in Iceland.

Medical records and cardiac imaging studies obtained between 1997 and 2010 were reviewed to identify Icelandic patients with HCM, who were subsequently invited for genetic studies. Mutation-positive individuals and their at-risk relatives were invited for additional studies. A total of 180 HCM patients were identified. Genetic analyses of 151 patients defined pathogenic mutations in 101 (67%). The vast majority of mutation-positive patients carried the same MYBPC3 mutation (c.927-2A>G). Familial screening of 225 at-risk relatives identified an additional 108 mutation carriers, of whom around 50% had HCM. HCM occured at an earlier age in males, but the lifetime penetrance appears to be high and equivalent in both males and females. Haplotype and genetic genealogical data defined MYBPC3 c.927-2A>G as a founder mutation that has been inherited through ~18 generations and has an estimated population prevalence of 0.36%.

Fabry disease, a rare lysosomal storage disease was identified as the cause of left ventricular hypertrophy in 8 individuals with prior HCM diagnosis (5%). Distinguishing these disorders is clinically important as enzyme replacement therapy may be considered to treat Fabry disease. Family screening identified additional 33 individuals with Fabry disease.

Um doktorsefni­
Berglind A­alsteinsdˇttir lauk st˙dentsprˇfi af nßtt˙rufrŠ­i- og e­lisfrŠ­ibraut Fj÷lbrautaskˇla Su­urnesja ßri­ 1999 og embŠttisprˇfi Ý lŠknisfrŠ­i frß Hßskˇla ═slands ßri­ 2006. H˙n lauk sÚrnßmi Ý almennum lyflŠkningum ßri­ 2015 og sÚrnßmi Ý hjartalŠkningum ■remur ßrum sÝ­ar. Frß ßrinu 2014 hefur Berglind starfa­ ß hjartadeild Haukeland hßskˇlasj˙krah˙ssins Ý Bergen Ý Noregi. Foreldrar Berglindar eru A­alsteinn K. Gu­mundsson og Au­ur H. Jˇnatansdˇttir. Eiginma­ur Berglindar er Arnar ١r Emilsson og eiga ■au dŠturnar K÷tlu MarÝu 8 ßra og Tinnu 3 ßra.


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