Presentation number: MG 36

INCOMPLETE PENETRANCE OF PATHOGENIC GREBL1 VARIANT CAUSED A DIFFERENT CLINICAL PRESENTATION IN 3 GENERATIONS OF ONE FAMILY

Martin Čemerin1, Petar Brlek1, Vid Matišić1, Vilim Molnar1, Ivana Erceg Ivkošić1,2, Dragan Primorac1,2,3,4,5,6,7,8,9,10

1St. Catherine Specialty Hospital, Zagreb, Croatia, 2Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia, 3Medical School, University of Rijeka, Rijeka, Croatia, 4Medical School, University of Mostar, Mostar, Bosnia and Herzegovina, 5Medical School, University of Split, Split, Croatia, 6Department of Biochemistry & Molecular Biology, The Pennsylvania State University, State College, PA, USA, 7The Henry C. Lee College of Criminal Justice and Forensic Sciences, University of New Haven, West Haven, CT, USA, 8Medical School REGIOMED, Coburg, Germany, 9School of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia, 10National Forensic Sciences University, Gujarat, India

Renal agenesis is a rare congenital malformation characterized by the complete absence of development of one or both kidneys. The prevalence of such malformation is estimated at around 1/2000 for unilateral and 1/8,500 for bilateral renal agenesis. Even though unilateral renal agenesis can often be detected as an incidental finding later in life, bilateral renal agenesis is unfortunately incompatible with life. Our patient previously had 2 failed pregnancies, both associated with urogenital malformations of the fetus. The patient had functional kidneys and no urogenital malformations even though her mother was diagnosed with unilateral renal agenesis and subsequent contralateral kidney hypertrophia and systemic hypertension. Her mother also had a miscarriage before our patient’s birth. Her brother is a healthy individual and her husband reports no inherited diseases on his side of the family. Considering the patient’s medical history, genetic testing was initiated in our hospital and included the “Invitae Congenital Anomalies of Kidney and Urinary Tract (CAKUT) Panel” which covers genes associated with congenital renal malformations. Even though these conditions can present with a seemingly similar phenotype, they are often associated with a high degree of genetic heterogeneity. Therefore, this broad panel testing allows for an efficient evaluation of several potential genes based on a single clinical indication. Results of the genetic testing revealed that the patient is a heterozygote for the pathogenic variant of the GREB1L gene (c.4115_4118dup (p.Trp1373Cysfs*4), associated with autosomal dominant renal hypodysplasia/aplasia. Preliminary evidence also correlates the GREBL1 gene with autosomal dominant inner ear malformations and deafness. It is important to note that the GREBL1 gene shows reduced penetration which was clearly evident by the absence of the symptoms in our patient despite the presence of the genetic mutation. In the case of our patient, there is a 50% chance that the pathogenic gene variant will be passed on to descendants. These findings further emphasize the importance of genetic testing which can be combined with prenatal ultrasonography to provide an optimal diagnostic evaluation.

Key words: renal agenesis, CAKUT, GREB1L, miscarriage, genetic testing

  • OPEN ACCESS

  • PEER REVIEWED

Published: June 21st, 2022;

Copyright: © 2022 ISABS & IAR Publishing. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.