E-viri
Recenzirano
Odprti dostop
-
Ruaud, Lyse; Rice, Gillian I.; Cabrol, Christelle; Piard, Juliette; Rodero, Mathieu; Eyk, Lien; Boucher‐Brischoux, Elise; Noordhout, Alain Maertens; Maré, Ricardo; Scalais, Emmanuel; Pauly, Fernand; Debray, François‐Guillaume; Dobyns, William; Uggenti, Carolina; Park, Ji Woo; Hur, Sun; Livingston, John H.; Crow, Yanick J.; Maldergem, Lionel
Human mutation, August 2018, Letnik: 39, Številka: 8Journal Article, Web Resource
We describe progressive spastic paraparesis in two male siblings and the daughter of one of these individuals. Onset of disease occurred within the first decade, with stiffness and gait difficulties. Brisk deep tendon reflexes and extensor plantar responses were present, in the absence of intellectual disability or dermatological manifestations. Cerebral imaging identified intracranial calcification in all symptomatic family members. A marked upregulation of interferon‐stimulated gene transcripts was recorded in all three affected individuals and in two clinically unaffected relatives. A heterozygous IFIH1 c.2544T>G missense variant (p.Asp848Glu) segregated with interferon status. Although not highly conserved (CADD score 10.08 vs. MSC‐CADD score of 19.33) and predicted as benign by in silico algorithms, this variant is not present on publically available databases of control alleles, and expression of the D848E construct in HEK293T cells indicated that it confers a gain‐of‐function. This report illustrates, for the first time, the occurrence of autosomal‐dominant spastic paraplegia with intracranial calcifications due to an IFIH1‐related type 1 interferonopathy. By describing a family where three individuals over two generations present progressive isolated spastic paraparesia, associated in one of them with extensive brain calcification on CT scan, we came to the conclusion that it relates to an IFIH1‐associated interferonopathy. Interestingly, prediction softwares were non‐contributive in establishing pathogenicity of the corresponding c.2445T>G missense variant, only demonstrated through a construct in HEK293T cells. Two relatives with a strong interferon signature were completely asymptomatic, illustrating how clinical expression can be highly variable in interferonopathies.
Avtor
![loading ... loading ...](themes/default/img/ajax-loading.gif)
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.