@article {931106, title = {Expansion of phenotype and genotypic data in CRB2-related syndrome.}, journal = {Eur J Hum Genet}, volume = {24}, number = {10}, year = {2016}, month = {2016 Oct}, pages = {1436-44}, abstract = {Sequence variants in CRB2 cause a syndrome with greatly elevated maternal serum alpha-fetoprotein and amniotic fluid alpha-fetoprotein levels, cerebral ventriculomegaly and renal findings similar to Finnish congenital nephrosis. All reported patients have been homozygotes or compound heterozygotes for sequence variants in the Crumbs, Drosophila, Homolog of, 2 (CRB2) genes. Variants affecting CRB2 function have also been identified in four families with steroid resistant nephrotic syndrome, but without any other known systemic findings. We ascertained five, previously unreported individuals with biallelic variants in CRB2 that were predicted to affect function. We compiled the clinical features of reported cases and reviewed available literature for cases with features suggestive of CRB2-related syndrome in order to better understand the phenotypic and genotypic manifestations. Phenotypic analyses showed that ventriculomegaly was a common clinical manifestation (9/11 confirmed cases), in contrast to the original reports, in which patients were ascertained due to renal disease. Two children had minor eye findings and one was diagnosed with a B-cell lymphoma. Further genetic analysis identified one family with two affected siblings who were both heterozygous for a variant in NPHS2 predicted to affect function and separate families with sequence variants in NPHS4 and BBS7 in addition to the CRB2 variants. Our report expands the clinical phenotype of CRB2-related syndrome and establishes ventriculomegaly and hydrocephalus as frequent manifestations. We found additional sequence variants in genes involved in kidney development and ciliopathies in patients with CRB2-related syndrome, suggesting that these variants may modify the phenotype.}, issn = {1476-5438}, doi = {10.1038/ejhg.2016.24}, author = {Lamont, Ryan E and Tan, Wen-Hann and Innes, A Micheil and Parboosingh, Jillian S and Schneidman-Duhovny, Dina and Rajkovic, Aleksandar and Pappas, John and Altschwager, Pablo and DeWard, Stephanie and Fulton, Anne and Gray, Kathryn J and Krall, Max and Mehta, Lakshmi and Rodan, Lance H and Saller, Devereux N and Steele, Deanna and Stein, Deborah and Yatsenko, Svetlana A and Bernier, Fran{\c c}ois P and Slavotinek, Anne M} }