Suchergebnisse

AbstractMeckel-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.

Massively parallel sequencing (MPS) technology has become increasingly available
and has been widely used to screen for trisomies 21, 18, and 13 in singleton
pregnancies. This study assessed the performance of MPS testing of cell-free
fetal DNA (cffDNA) from maternal plasma for trisomies 21, 18, and 13 in twin
pregnancies. Ninety-two women with twin pregnancies were recruited. The results
were identified through karyotypes of amniocentesis or clinical examination and
follow-up of the neonates. Fluorescent in-situ hybridization was used to examine
the placentas postnatally in cases of false-positive results. The fetuses with
autosomal trisomy 21 (n = 2) and trisomy 15 (n
= 1) were successfully detected via MPS testing of cffDNA. There was one
false-positive for trisomy 13 (n = 1), and fluorescence in-situ
hybridization (FISH) identified confined placental mosaicism in this case. For
twin pregnancies undergoing second-trimester screening for trisomy, MPS testing
of cffDNA is feasible and can enhance the diagnostic spectrum of non-invasive
prenatal testing, which could effectively reduce invasive prenatal diagnostic
methods. In addition to screening for trisomy 21, 18, and 13 by cffDNA, MPS can
detect fetal additional autosomal trisomy. False-positive results cannot
completely exclude confined placental mosaicism.