Hereditary hyperferritinemia-cataract syndrome in three Czech families: molecular genetic testing and clinical implications

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F20%3A10417803" target="_blank" >RIV/00216208:11130/20:10417803 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064203:_____/20:10417803 RIV/00216208:11110/20:10417803 RIV/00064165:_____/20:10417803

Výsledek na webu

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

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jaapos.2020.07.014" target="_blank" >10.1016/j.jaapos.2020.07.014</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Hereditary hyperferritinemia-cataract syndrome in three Czech families: molecular genetic testing and clinical implications

Popis výsledku v původním jazyce

BACKGROUND: Hereditary hyperferritinemia-cataract syndrome (HHCS) is an autosomal dominant disorder manifesting with high serum ferritin levels and the formation of early-onset cataracts, with numerous small opacities, predominantly in the lens cortex. HHCS is caused by mutations in the iron-responsive element of the FTL gene. The aim of this study was to establish a molecular diagnosis in three Czech probands with suspected HHCS. METHODS: A complex ocular and systemic evaluation, including ferritin and iron measurements, was performed. The 5&apos; untranslated region of FTL was directly sequenced in all available family members, followed by paternity testing in one family. RESULTS: Three different FLT pathogenic variants (c.-161C&gt;T, c.-167C&gt;T, and c.-168G&gt;C) present in the heterozygous state were detected in each of the 3 probands. Two segregated with the disease phenotype within the families, but c.-167C&gt;T occurred de novo (confirmed by paternity testing). Prior to establishing molecular diagnosis, two probands were misdiagnosed with hemochromatosis. One individual, aged 43 years, underwent phlebotomy; another, aged 8.5 years, was treated with the iron chelator deferasirox, leading to life-threatening acute hyperammonemia, without severe liver injury. CONCLUSIONS: Lack of family history does not exclude HHCS, because the pathogenic variant can arise de novo. Noncoding regions are often omitted from diagnostic gene panels, thus evading detection. Careful clinical evaluations and targeted genetic screening are important for avoiding potentially harmful treatments.

Název v anglickém jazyce

Hereditary hyperferritinemia-cataract syndrome in three Czech families: molecular genetic testing and clinical implications

Popis výsledku anglicky

BACKGROUND: Hereditary hyperferritinemia-cataract syndrome (HHCS) is an autosomal dominant disorder manifesting with high serum ferritin levels and the formation of early-onset cataracts, with numerous small opacities, predominantly in the lens cortex. HHCS is caused by mutations in the iron-responsive element of the FTL gene. The aim of this study was to establish a molecular diagnosis in three Czech probands with suspected HHCS. METHODS: A complex ocular and systemic evaluation, including ferritin and iron measurements, was performed. The 5&apos; untranslated region of FTL was directly sequenced in all available family members, followed by paternity testing in one family. RESULTS: Three different FLT pathogenic variants (c.-161C&gt;T, c.-167C&gt;T, and c.-168G&gt;C) present in the heterozygous state were detected in each of the 3 probands. Two segregated with the disease phenotype within the families, but c.-167C&gt;T occurred de novo (confirmed by paternity testing). Prior to establishing molecular diagnosis, two probands were misdiagnosed with hemochromatosis. One individual, aged 43 years, underwent phlebotomy; another, aged 8.5 years, was treated with the iron chelator deferasirox, leading to life-threatening acute hyperammonemia, without severe liver injury. CONCLUSIONS: Lack of family history does not exclude HHCS, because the pathogenic variant can arise de novo. Noncoding regions are often omitted from diagnostic gene panels, thus evading detection. Careful clinical evaluations and targeted genetic screening are important for avoiding potentially harmful treatments.

Druh

J_SC - Článek v periodiku v databázi SCOPUS

CEP obor

—

OECD FORD obor

10600 - Biological sciences

Projekt

<a href="/cs/project/NV17-30500A" target="_blank" >NV17-30500A: Kongenitalni katarakty - využití metod sekvenování nové generace v diagnostickém a léčebném algoritmu</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus

ISSN

1091-8531

e-ISSN

—

Svazek periodika

24

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

5

Strana od-do

"352e1"-"352e5"

Kód UT WoS článku

—

EID výsledku v databázi Scopus

2-s2.0-85097470265