Genetic Counseling and Assisted Reproductive Technologies.

Despite the ever-increasing number of patients undergoing fertility treatments and the expanded use of genetic testing in this context, there has been limited focus in the literature on the involvement of genetics professionals in the assisted reproductive technology (ART) setting. Here we discuss the importance of genetic counseling within reproductive medicine. We review how genetic testing of embryos is performed, the process of gamete donation, the challenges associated with genetic testing, and the complexities of genetic test result interpretation.

CRB2 mutations produce a phenotype resembling congenital nephrosis, Finnish type, with cerebral ventriculomegaly and raised alpha-fetoprotein.

We report five fetuses and a child from three families who shared a phenotype comprising cerebral ventriculomegaly and echogenic kidneys with histopathological findings of congenital nephrosis. The presenting features were greatly elevated maternal serum alpha-fetoprotein (MSAFP) or amniotic fluid alpha-fetoprotein (AFAFP) levels or abnormalities visualized on ultrasound scan during the second trimester of pregnancy. Exome sequencing revealed deleterious sequence variants in Crumbs, Drosophila, Homolog of, 2 (CRB2) consistent with autosomal-recessive inheritance. Two fetuses with cerebral ventriculomegaly and renal microcysts were compound heterozygotes for p.Asn800Lys and p.Trp759Ter, one fetus with renal microcysts was a compound heterozygote for p.Glu643Ala and p.Asn800Lys, and one child with cerebral ventriculomegaly, periventricular heterotopias, echogenic kidneys, and renal failure was homozygous for p.Arg633Trp in CRB2. Examination of the kidneys in one fetus showed tubular cysts at the corticomedullary junction and diffuse effacement of the epithelial foot processes and microvillous transformation of the renal podocytes, findings that were similar to those reported in congenital nephrotic syndrome, Finnish type, that is caused by mutations in nephrin (NPHS1). Loss of function for crb2b and nphs1 in Danio rerio were previously shown to result in loss of the slit diaphragms of the podocytes, leading to the hypothesis that nephrosis develops from an inability to develop a functional glomerular barrier. We conclude that the phenotype associated with CRB2 mutations is pleiotropic and that the condition is an important consideration in the evaluation of high MSAFP/AFAFP where a renal cause is suspected.