Genome sequencing identifies three molecular diagnoses including a mosaic variant in the COL2A1 gene in an individual with Pol III-related leukodystrophy and Feingold syndrome.
Cold Spring Harb Mol Case Stud
; 7(6)2021 12.
Article
en En
| MEDLINE
| ID: mdl-34737199
ABSTRACT
Undiagnosed genetic disease imposes a significant burden on families and health-care resources, especially in cases with a complex phenotype. Here we present a child with suspected leukodystrophy in the context of additional features, including hearing loss, clinodactyly, rotated thumbs, tapered fingers, and simplified palmar crease. Trio genome sequencing (GS) identified three molecular diagnoses in this individual compound heterozygous missense variants associated with polymerase III (Pol III)-related leukodystrophy, a 4-Mb de novo copy-number loss including the MYCN gene associated with Feingold syndrome, and a mosaic single-nucleotide variant associated with COL2A1-related disorders. These variants fully account for the individual's features, but also illustrate the potential for superimposed and unclear contributions of multiple diagnoses to an individual's overall presentation. This report demonstrates the advantage of GS in detection of multiple variant types, including low-level mosaic variants, and emphasizes the need for comprehensive genetic analysis and detailed clinical phenotyping to provide individuals and their families with the maximum benefit for clinical care and genetic counseling.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fístula Traqueoesofágica
/
Deformidades Congénitas de las Extremidades
/
Discapacidad Intelectual
/
Microcefalia
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cold Spring Harb Mol Case Stud
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos