Genetic and preimplantation diagnosis of cystic kidney disease with ventriculomegaly

J Hum Genet. 2020 May;65(5):455-459. doi: 10.1038/s10038-020-0731-0. Epub 2020 Feb 13.

Abstract

Ventriculomegaly with cystic kidney disease (VMCKD) is a rare and severe disorder characterized by cerebral ventriculomegaly, greatly elevated maternal serum alpha-fetoprotein (MSAFP) or amniotic fluid alpha-fetoprotein (AFAFP) levels and kidney disease similar to Finnish congenital nephrosis. Recessive mutations in the CRB2 (NM_173689) gene have been shown to cause the syndrome. Here, we described a nonconsanguineous Chinese family with two fetuses affected with VMCKD. A novel compound heterozygous mutation was identified in the CRB2 gene with co-segregation. One mutation [c.1960G>C (p.A654P)] was inherited from the father, while another mutation [c.3078_c.3093delGGCGCGGCCCCGGCCC (p.L1026Lfs*110)] was inherited from the mother. Preimplantation genetic testing for monogenic disease (PGT-M) was performed for the carrier couple with full informed consent and successfully blocked the inheritance of the disease. Our study has important implications on molecular diagnosis and genetic counseling for VMCKD and extends the mutation spectrum in CRB2 gene.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Carrier Proteins / genetics*
  • Female
  • Genetic Testing*
  • Humans
  • Hydrocephalus* / diagnosis
  • Hydrocephalus* / genetics
  • Kidney Diseases, Cystic* / diagnosis
  • Kidney Diseases, Cystic* / genetics
  • Male
  • Membrane Proteins / genetics*
  • Mutation*
  • Pregnancy
  • Preimplantation Diagnosis*

Substances

  • CRB2 protein, human
  • Carrier Proteins
  • Membrane Proteins

Supplementary concepts

  • Cystic Kidney Disease with Ventriculomegaly