Browse by author
Lookup NU author(s): Mohamed Al-Hamed, Professor John SayerORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
© 2020, Italian Society of Nephrology. Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT) are a group of abnormalities that affect structure of the kidneys or other structures of the urinary tract. The majority of CAKUT are asymptomatic and are diagnosed prenatally by ultrasound scanning or found incidentally in postnatal life. CAKUT varies in severity and may lead to life-threatening kidney failure and end-stage kidney disease. Renal agenesis, a severe form of CAKUT, is a congenital absence of one or both kidneys. Bilateral renal agenesis belongs to a group of prenatally lethal renal diseases and is often detected on fetal ultrasound scanning during the investigation of oligohydramnios. Approximately 40% of fetuses with bilateral renal agenesis are stillborn or die a few hours postnatally. Mutations in many renal development genes have been shown to be associated with renal agenesis. Methods: Six consanguineous Saudi Arabian families were recruited to study the molecular genetic causes of recurrent miscarriages and lost fetuses due to oligohydramnios, renal agenesis and other congenital anomalies. Whole exome sequencing was employed to underlying detect genetic defects. Results: Novel loss of function variants were detected in FRAS1 and FREM2. In FRAS1, a homozygous splice site variant c.9780+2T>C was found in an affected fetus, segregating form each parent. In addition, in three other families both parents were heterozygous for a frameshift variant (c.8981dupT; p.His2995Profs*3) and splice site variants (c.5217+1G>C and c.8098+2T>A), respectively. In FREM2, a homozygous nonsense variant (c.2303C>G; p.Ser768*) was found in an affected fetus, segregating from both parents. In another family, both parents carried a FREM2 heterozygous frameshift variant (c.3969delC; p.Asn1323Lysfs*5). Conclusion: We describe consanguineous families with clinical features of antenatal oligohydramnios and bilateral renal agenesis, in whom we have identified novel pathogenic variants in FRAS1 and FREM2. These finding highlights the association between mutations in FRAS1 and FREM2 and antenatal/perinatal death.
Author(s): Al-Hamed MH, Sayer JA, Alsahan N, Tulbah M, Kurdi W, Ambusaidi Q, Ali W, Imtiaz F
Publication type: Article
Publication status: Published
Journal: Journal of Nephrology
Year: 2021
Volume: 34
Pages: 893-900
Print publication date: 01/06/2021
Online publication date: 08/07/2020
Acceptance date: 02/07/2020
ISSN (print): 1121-8428
ISSN (electronic): 1724-6059
Publisher: Springer Nature
URL: https://doi.org/10.1007/s40620-020-00795-0
DOI: 10.1007/s40620-020-00795-0
Altmetrics provided by Altmetric
