Triple diagnosis of Wiedemann-Steiner, Waardenburg and DLG3-related intellectual disability association found by WES: A case report.
J Gene Med
; 22(8): e3197, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32246869
ABSTRACT
BACKGROUND:
The development of whole-exome sequencing (WES) and whole-genome sequencing (WGS) for clinical purposes now allows the identification of multiple pathogenic variants in patients with a rare disease. This occurs even when a single causative gene was initially suspected. We report the case of an 8-year-old patient with global developmental delays and dysmorphic features, with a possibly pathogenic variant in three distinct genes.METHODS:
Trio-based exome sequencing was performed by IntegraGen SA (Evry, France), on an Illumina HiSeq4000 (Illumina, San Diego, CA, USA). Sanger sequencing was performed to confirm the variants that were found.RESULTS:
WES showed the presence of three possibly deleterious variants KMT2A c.9068delA;p.Gln3023Argfs*3 de novo, PAX3 c.530C>G;p.Ala177Gly de novo and DLG3 c.127delG;p.Asp43Metfs*22 hemizygous inherited from the mother. KMT2A pathogenic variants are involved in Wiedemann-Steiner syndrome, and PAX3 is the gene responsible for Waardenburg syndrome. DLG3 variants have been described in a non-syndromic X-related intellectual disability.CONCLUSIONS:
Considering the dysmorphic features and intellectual disability presented by this patient, these three variants were imputed as pathogenic and their association was considered responsible for his phenotype. Dual molecular diagnoses have already been found by WES in several cohorts with an average of diagnostic yield of 7%. This case demonstrates and reminds us of the importance of analyzing exomes rigorously and exhaustively because, in some cases (< 10%), it can explain superimposed traits or blended phenotypes.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Waardenburg
/
Anormalidades Múltiplas
/
Deficiência Intelectual
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Child
/
Humans
/
Male
Idioma:
En
Revista:
J Gene Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
França