Identification of pathogenic deep intronic variant and exonic LINE-1 insertion in a patient with Meckel syndrome.
Ann Hum Genet
; 87(4): 196-202, 2023 07.
Article
en En
| MEDLINE
| ID: mdl-36970932
ABSTRACT
Biallelic CC2D2A variants are associated with a wide range of neurodevelopmental disorders including Meckel syndrome. Here we report a Japanese girl with Meckel syndrome harboring a pathogenic deep intronic variant (NM_001378615.1c.1149+3569A>G) and an exonic LINE-1 insertion, which was predicted to cause aberrant splicing by SpliceAI and was detected by TEMP2 program, respectively. RNA analysis using urine-derived cells (UDCs) showed retention of 149-bp intronic sequences, leading to frameshift. Immunoblotting showed marked reduction of CC2D2A protein in the patient. Our report demonstrated that utilization of transposon detection tool and functional analysis using UDCs will increase diagnostic yield of genome sequencing.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Empalme del ARN
Tipo de estudio:
Diagnostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Ann Hum Genet
Año:
2023
Tipo del documento:
Article
País de afiliación:
Japón