Three Novel Variants of CEP290 and CC2D2DA and a Link Between ZNF77 and SHH Signaling Pathway Are Found in Two Meckel-Gruber Syndrome Fetuses.
Reprod Sci
; 29(8): 2322-2332, 2022 08.
Article
en En
| MEDLINE
| ID: mdl-34981460
Meckel-Gruber syndrome (MKS) is a rare lethal autosomal recessive inherited disorder. Missed diagnosis might happen in clinical works due to an unclear genotype-phenotype correlation. We analyzed two families visiting our center; the parents are normal; each of the family aborted a fetus at 12WG. Following ultrasonography and pathological examination, both were diagnosed as MKS. Whole exome sequencing identified a compound heterozygous of two novel variants of CEP290 and a heterozygous of a novel variant of CC2D2A. Frameshift mutations in ZNF77 were also detected. Western blot analyzing whole-brain tissue showed that the expression of ZNF77, CC2D2A, and CEP290 was enhanced. HEK293T transfected with over-expression wildtype/mutated ZNF77 plasmid showed that SHH was increased in wildtype ZNF77 cells, while SHH and CC2D2A were increased in mutated ZNF77 cells. Our research provided two novel pathogenic variants of CEP290 and CC2D2A and suggested that ZNF77 might promote the expression of CC2D2A and regulate the amount of SHH.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Retinitis Pigmentosa
/
Trastornos de la Motilidad Ciliar
/
Proteínas del Citoesqueleto
/
Encefalocele
/
Enfermedades Renales Poliquísticas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Reprod Sci
Asunto de la revista:
MEDICINA REPRODUTIVA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos