Novel compound heterozygous variants in NHLRC2 in a patient with FINCA syndrome.
J Hum Genet
; 65(10): 911-915, 2020 Oct.
Article
em En
| MEDLINE
| ID: mdl-32435055
ABSTRACT
Two variants in the ubiquitously expressed NHLRC2 gene have been reported to cause a lethal fibrotic cerebropulmonary disease termed fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome in three Finnish children. Our objective was to determine the genetic basis of disease in a new patient with clinical features of FINCA syndrome using whole-exome sequencing (WES) and confirmation by Sanger sequencing. The patient has one known and one novel variant in NHLRC2 (c.442T>G, p.D148Y and c.428C>A, p.H143P, respectively). p.H143P is extremely rare and is not present in the gnomAD database of >140,000 allele sequences from healthy humans. Both variants affect the highly conserved N-terminal thioredoxin (Trx)-like domain of NHLRC2 and are predicted to be damaging. We conclude that a compound heterozygous combination of a known and a novel variant in NHLRC2 causes FINCA syndrome in a 2-year-old Ukrainian patient, underscoring the importance of NHLRC2 as a central regulator of fibrosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Mutação Puntual
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Cardiomegalia
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Doenças Neurodegenerativas
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Peptídeos e Proteínas de Sinalização Intracelular
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Angiomatose
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Pneumopatias
Limite:
Child, preschool
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article