Komrower Memorial Lecture 2023. Molecular basis of phenotype expression in homocystinuria: Where are we 30 years later?

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F24%3A10481348" target="_blank" >RIV/00216208:11110/24:10481348 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/24:10481348

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Ki1HW0mOze" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Ki1HW0mOze</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/jimd.12767" target="_blank" >10.1002/jimd.12767</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Komrower Memorial Lecture 2023. Molecular basis of phenotype expression in homocystinuria: Where are we 30 years later?

Popis výsledku v původním jazyce

This review summarises progress in the research of homocystinuria (HCU) in the past three decades. HCU due to cystathionine β-synthase (CBS) was discovered in 1962, and Prof. Jan Peter Kraus summarised developments in the field in the first-ever Komrower lecture in 1993. In the past three decades, significant advancements have been achieved in the biology of CBS, including gene organisation, tissue expression, 3D structures, and regulatory mechanisms. Renewed interest in CBS arose in the late 1990s when this enzyme was implicated in biogenesis of H2S. Advancements in genetic and biochemical techniques enabled the identification of several hundreds of pathogenic CBS variants and the misfolding of missense mutations as a common mechanism. Several cellular, invertebrate and murine HCU models allowed us to gain insights into functional and metabolic pathophysiology of the disease. Establishing the E-HOD consortium and patient networks, HCU Network Australia and HCU Network America, offered new possibilities for acquiring clinical data in registries and data on patients&apos; quality of life. A recent analysis of data from the E-HOD registry showed that the clinical variability of HCU is broad, extending from severe childhood disease to milder (late) adulthood forms, which typically respond to pyridoxine. Pyridoxine responsiveness appears to be the key factor determining the clinical course of HCU. Increased awareness about HCU played a role in developing novel therapies, such as gene therapy, correction of misfolding by chaperones, removal of methionine from the gut and enzyme therapies that decrease homocysteine or methionine in the circulation.

Název v anglickém jazyce

Komrower Memorial Lecture 2023. Molecular basis of phenotype expression in homocystinuria: Where are we 30 years later?

Popis výsledku anglicky

This review summarises progress in the research of homocystinuria (HCU) in the past three decades. HCU due to cystathionine β-synthase (CBS) was discovered in 1962, and Prof. Jan Peter Kraus summarised developments in the field in the first-ever Komrower lecture in 1993. In the past three decades, significant advancements have been achieved in the biology of CBS, including gene organisation, tissue expression, 3D structures, and regulatory mechanisms. Renewed interest in CBS arose in the late 1990s when this enzyme was implicated in biogenesis of H2S. Advancements in genetic and biochemical techniques enabled the identification of several hundreds of pathogenic CBS variants and the misfolding of missense mutations as a common mechanism. Several cellular, invertebrate and murine HCU models allowed us to gain insights into functional and metabolic pathophysiology of the disease. Establishing the E-HOD consortium and patient networks, HCU Network Australia and HCU Network America, offered new possibilities for acquiring clinical data in registries and data on patients&apos; quality of life. A recent analysis of data from the E-HOD registry showed that the clinical variability of HCU is broad, extending from severe childhood disease to milder (late) adulthood forms, which typically respond to pyridoxine. Pyridoxine responsiveness appears to be the key factor determining the clinical course of HCU. Increased awareness about HCU played a role in developing novel therapies, such as gene therapy, correction of misfolding by chaperones, removal of methionine from the gut and enzyme therapies that decrease homocysteine or methionine in the circulation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

<a href="/cs/project/NU23-07-00383" target="_blank" >NU23-07-00383: Vzácné poruchy metabolismu sirných aminokyselin: nové diagnostické postupy a detailní fenotypové projevy (RADISUM)</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Inherited Metabolic Disease

ISSN

0141-8955

e-ISSN

1573-2665

Svazek periodika

47

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

19

Strana od-do

841-859

Kód UT WoS článku

001246889800001

EID výsledku v databázi Scopus

2-s2.0-85195808439