E-viri
Recenzirano
Odprti dostop
-
Rodríguez‐García, María Elena; Cotrina‐Vinagre, Francisco Javier; Bellusci, Marcello; Hernández‐Sánchez, Laura; Aragón, Ana Martínez; López‐Laso, Eduardo; Martín‐Hernández, Elena; Martínez‐Azorín, Francisco
Human mutation, October 2022, 2022-10-00, 20221001, Letnik: 43, Številka: 10Journal Article
We report the clinical and genetic features of a Caucasian girl who presented a severe neurodevelopmental disorder with drug‐resistant epilepsy, hypotonia, severe gastro‐esophageal reflux and brain magnetic resonance imaging anomalies. WES uncovered a novel variant in homozygosis (g.197092814_197092824delinsC) in HECW2 gene that encodes the E3 ubiquitin‐protein ligase HECW2. This protein induces ubiquitination and is implicated in the regulation of several important pathways involved in neurodevelopment and neurogenesis. Furthermore, de novo heterozygous missense variants in this gene have been associated with neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL). The homozygous variant of our patient disrupts the splice donor site of intron 22 and causes the elimination of exon 22 (r.3766_3917+1del) leading to an in‐frame deletion of the protein (p.Leu1256_Trp1306del). Functional studies showed a twofold increase of its RNA expression, while the protein expression level was reduced by 60%, suggesting a partial loss‐of‐function mechanism of pathogenesis. Thus, this is the first patient with NDHSAL caused by an autosomal recessive splicing variant in HECW2. This study identified the first patient with NDHSAL caused by an autosomal recessive splicing variant in HECW2 gene. The novel variant in homozygosis (g.197092814_197092824delinsC) produces the elimination of exon 22 (r.3765_3917del) leading to an in‐frame deletion of the protein (p.Leu1256_Trp1306del) and a 60% reduction in its expression level.
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.