{"id":6409,"date":"2026-10-19T09:48:52","date_gmt":"2026-10-19T09:48:52","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-sara-tholl-halldorsdottir\/"},"modified":"2026-10-19T09:48:52","modified_gmt":"2026-10-19T09:48:52","slug":"doktorsvorn-i-lif-og-laeknavisindum-sara-tholl-halldorsdottir","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-sara-tholl-halldorsdottir\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum Sara \u00de\u00f6ll Halld\u00f3rsd\u00f3ttir"},"content":{"rendered":"<div class=\"field-items\">\n<div class=\"field-item even\" property=\"content:encoded\">\n<p>\u00deri\u00f0judaginn 24. j\u00fan\u00ed 2025 ver Sara \u00de\u00f6ll Halld\u00f3rsd\u00f3ttir doktorsritger\u00f0 s\u00edna \u00ed l\u00edf- og l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands. Ritger\u00f0in ber heiti\u00f0: Inns\u00fdn \u00ed hlutverk KMT2D \u00ed Kabuki heilkenni 1. Mechanistic insights into the role of KMT2D in Kabuki syndrome 1.\u00a0<\/p>\n<p>Andm\u00e6lendur eru dr. Giuseppe Merla, pr\u00f3fessor vi\u00f0 University of Naples Federico II, Nap\u00f3l\u00ed,\u00a0 og Siddarth Banka, pr\u00f3fessor vi\u00f0 University of Manchester.\u00a0\u00a0<\/p>\n<p>Umsj\u00f3narkennari og lei\u00f0beinandi var Hans T\u00f3mas Bj\u00f6rnsson, pr\u00f3fessor. Auk hans s\u00e1tu \u00ed doktorsnefnd Erna Magn\u00fasd\u00f3ttir, d\u00f3sent, Gu\u00f0mundur L. Nor\u00f0dahl, verkefnastj\u00f3ri, Gregg Semenza, pr\u00f3fessor og Jill A. Fahrner, lektor.\u00a0\u00a0<\/p>\n<p>\u00de\u00f3rarinn Gu\u00f0j\u00f3nsson, pr\u00f3fessor og\u00a0 deildarforseti L\u00e6knadeildar, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0asal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 13.00.\u00a0<\/p>\n<p>\u00c1grip\u00a0<\/p>\n<p>Kabuki heilkenni af ger\u00f0 1 (KS1) er sjaldg\u00e6fur erf\u00f0asj\u00fakd\u00f3mur sem orsakast af arfblendnum st\u00f6kkbreytingum \u00ed Lysi\u0301n Mety\u0301ltransferasa 2D (KMT2D). \u00de\u00f3 a\u00f0 kl\u00edn\u00edsk einkenni geti veri\u00f0 breytileg eru einstaklingar me\u00f0 KS1 oft me\u00f0 s\u00e9rst\u00e6\u00f0a andlitsdr\u00e6tti, \u00feroskasker\u00f0ingu og vaxtarsker\u00f0ingu &#8211; sem endurspeglar \u00e1hrif heilkennisins \u00e1 m\u00f6rg l\u00edff\u00e6rakerfi. Meginmarkmi\u00f0 \u00feessarar ritger\u00f0ar var a\u00f0 d\u00fdpka skilning \u00e1 KMT2D \u00ed meinger\u00f0 sj\u00fakd\u00f3msins. \u00cd \u00feessari ranns\u00f3kn er n\u00fdtt m\u00fasal\u00edkan kynnt sem ber sj\u00faklingas\u00e9rt\u00e6ka mislestursbreytingu og s\u00fdnir helstu einkenni KS \u00e1samt n\u00fdrri svipger\u00f0 \u00fear sem \u00ed m\u00f6rgum KS d\u00fdranna mynda\u00f0ist a\u00f0eins eitt n\u00fdra. \u00cd brj\u00f3skfrumul\u00edkani \u00fear sem KMT2D hefur veri\u00f0 slegi\u00f0 \u00fat er s\u00fdnt fram \u00e1 a\u00f0 tap \u00e1 KMT2D sker\u00f0ir starfsemi hvatbera og eykur oxunar\u00e1lag, sem lei\u00f0ir til trufla\u00f0rar \u00feroskunar brj\u00f3skfrumna. S\u00fdnt er a\u00f0 h\u00e6gt er a\u00f0 koma \u00ed veg fyrir \u00feessa snemmb\u00e6ru \u00feroskun me\u00f0 \u00fev\u00ed a\u00f0 minnka oxunar\u00e1lag, sem bendir til m\u00f6gulegra tengsla milli trufla\u00f0rar starfsemi hvatbera og bein\u00feroska \u00ed KS1. CUT&amp;RUN og pr\u00f3teinranns\u00f3knir g\u00e1fu einnig til kynna a\u00f0 KMT2D hafi samverkun vi\u00f0 umritunar\u00fe\u00e1ttinn E2F4, sem tekur \u00fe\u00e1tt \u00ed stj\u00f3rnun frumuskiptingar og efnaskipta. \u00deessar ni\u00f0urst\u00f6\u00f0ur undirstrika mikilv\u00e6gt hlutverk KMT2D \u00ed \u00feroskun l\u00edff\u00e6ra, s\u00e9rstaklega \u00ed brj\u00f3skfrumum \u00fear sem \u00fea\u00f0 gegnir lykilhlutverki \u00ed stj\u00f3rnun hvatberaefnaskipta.\u00a0<\/p>\n<p>Abstract\u00a0<\/p>\n<p>Kabuki syndrome type 1 (KS1) is a rare genetic disorder caused by pathogenic variants in the Lysine Methyltransferase 2D (KMT2D). While clinical manifestations vary, individuals with KS1 commonly present with distinctive facial features, intellectual disability, and growth deficiency &#8211; reflecting the syndrome\u2019s multi-organ involvement. The main goal of this thesis was to deepen our understanding of KMT2D in disease pathogenesis. This study presents a novel mouse model carrying a patient-specific missense variant which displays core KS features in addition to a novel phenotype of unilateral renal agenesis. In a KMT2D-deficient chondrocyte model, we demonstrate that KMT2D loss impairs mitochondrial metabolism and increases oxidative stress, leading to disrupted chondrocyte differentiation. Notably, we show that this precocious differentiation is reversible by reducing oxidative stress, highlighting a potential mechanistic link between mitochondrial dysfunction and skeletal abnormalities in KS1. CUT&amp;RUN and protein analysis further indicate that KMT2D interacts with the transcription factor E2F4 which is involved in cell cycle regulation and metabolism. These findings highlight a critical role of KMT2D in organ development and particularly in skeletal development via metabolic regulation.\u00a0<\/p>\n<p>Um doktorsefni\u00f0\u00a0<\/p>\n<p>Sara \u00de\u00f6ll Halld\u00f3rsd\u00f3ttir er f\u00e6dd \u00e1ri\u00f0 1993 \u00e1 Akureyri. H\u00fan \u00fatskrifa\u00f0ist af n\u00e1tt\u00farufr\u00e6\u00f0ibraut Menntask\u00f3lans \u00e1 Egilsst\u00f6\u00f0um \u00e1ri\u00f0 2013. Sara lauk B.Sc.-pr\u00f3fi \u00ed l\u00edfeindafr\u00e6\u00f0i fr\u00e1 H\u00e1sk\u00f3la \u00cdslands \u00e1ri\u00f0 2016 og meistarapr\u00f3fi, einnig \u00ed l\u00edfeindafr\u00e6\u00f0i, \u00e1ri\u00f0 2018, me\u00f0 verkefni hj\u00e1 sprotafyrirt\u00e6kinu Platome l\u00edft\u00e6kni. Eftir \u00fatskrift h\u00f3f Sara st\u00f6rf sem verkefnastj\u00f3ri \u00e1 ranns\u00f3knarstofu dr. Hans T\u00f3masar Bj\u00f6rnssonar og innrita\u00f0ist s\u00ed\u00f0an \u00ed doktorsn\u00e1m hj\u00e1 honum \u00e1ri\u00f0 2020. Foreldrar hennar eru El\u00edn Sigr\u00ed\u00f0ur Einarsd\u00f3ttir og Halld\u00f3r J\u00f3n Halld\u00f3rsson. Maki S\u00f6ru er Fri\u00f0rik Ingi \u00der\u00e1insson og saman eiga \u00feau Benjam\u00edn \u00de\u00f3r Fri\u00f0riksson,2 \u00e1ra.\u00a0<\/p>\n<\/div><\/div>","protected":false},"featured_media":5772,"template":"","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"_phd_date_start":"2025-06-24T13:00:00+00:00","_phd_date_end":"2025-06-24T16:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"Inns\u00fdn \u00ed hlutverk KMT2D \u00ed Kabuki heilkenni 1. 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