Functional validation of a novel AAAS variant in an atypical presentation of Allgrove syndrome.
Mol Genet Genomic Med
; 10(7): e1966, 2022 07.
Article
en En
| MEDLINE
| ID: mdl-35570467
ABSTRACT
BACKGROUND:
Achalasia-addisonianism-alacrima syndrome, frequently referred to as Allgrove syndrome or Triple A syndrome, is a multisystem disorder resulting from homozygous or compound heterozygous pathogenic variants in the gene encoding aladin (AAAS). Aladin is a member of the WD-repeat family of proteins and is a component of the nuclear pore complex. It is thought to be involved in nuclear import and export of molecules. Here, we describe an individual with a paternally inherited truncating variant and a maternally inherited, novel missense variant in AAAS presenting with alacrima, achalasia, anejaculation, optic atrophy, muscle weakness, dysarthria, and autonomic dysfunction.METHODS:
Whole-exome sequencing was performed in the proband, sister, and parents. Variants were confirmed by Sanger sequencing. The localization of aladin to the nuclear pore was assessed in cells expressing the patient variant.RESULTS:
Functional testing of the maternally inherited variant, p.(Arg270Pro), demonstrated decreased localization of aladin to the nuclear pore in cells expressing the variant, indicating a deleterious effect. Follow-up testing in the proband's affected sister revealed that she also inherited the biallelic AAAS variants.CONCLUSIONS:
Review of the patient's clinical, pathological, and genetic findings resulted in a diagnosis of Triple A syndrome.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Acalasia del Esófago
/
Insuficiencia Suprarrenal
Límite:
Female
/
Humans
Idioma:
En
Revista:
Mol Genet Genomic Med
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos