Journal Article

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome

Deng, Rong, Casolari, Emilio, Sampson, Matthew G, Jeanpierre, Cecile, Cusi, Daniele, Mizerska-Wasiak, Malgorzata, Krzemien, Grazyna, Katsanis, Nicholas, Martino, Jeremiah, Liu, Yangfan P, Izzi, Claudia, Sikora, Przemyslaw, Morrow, Bernice E, Tasic, Velibor, Drozdz, Dorota, Arapovic, Adela, Racedo, Silvia E, Latos-Bielenska, Anna, Darlow, John M, Drummond, Iain A, Lozanovski, Vladimir J, Yan, Zhonghai, Werth, Max, Mitrotti, Adele, Gucev, Zoran, Warady, Bradley A, Allegri, Landino, Papaioannou, Virginia E, Flogelova, Hana, Carpentier, Wassila, Kunac, Nenad, Szczepanska, Maria, Salomon, Rémi, Capone, Valentina P, Materna-Kiryluk, Anna, Puri, Prem, Steers, Nicholas J, Honig, Barry, Otto, Edgar A, Makar, Gabriel S, Miklaszewska, Monika, Ghiggeri, Gian Marco, Maiorana, Mariarosa, Szmigielska, Agnieszka, Liu, Qingxue, Zaniew, Marcin, Vukojevic, Katarina, Hildebrandt, Friedhelm, Carrea, Alba, Lopez-Rivera, Esther, Zackai, Elaine H, Imamoto, Akira, Gillies, Christopher E, Anderson, Blair R, Heidet, Laurence, Furth, Susan L, Sanna-Cherchi, Simone, Vivante, Asaf, Hakonarson, Hakon, Gaillard, Dominique, Saraga, Mar

2017

Overview

A third of patients with the DiGeorge syndrome have congenital kidney and urinary tract anomalies. This study provides evidence that haploinsufficiency of CRKL is associated with such anomalies in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Deletions on chromosome 22q11.2 are the most common cause of the DiGeorge syndrome (Online Mendelian Inheritance in Man [OMIM] number, 188400) and the velocardiofacial syndrome (OMIM number, 192430) and constitute the most common microdeletion disorder in humans, with an estimated prevalence of 1 in 2000 to 4000 live births. 1 – 3 The DiGeorge syndrome is a debilitating, multisystemic condition that features (with variable expressivity) cardiac malformations, velopharyngeal insufficiency, hypoparathyroidism with hypocalcemia, and thymic aplasia with immune deficiency. Additional phenotypes include neurodevelopmental defects and urogenital malformations. 4 – 7 The long arm of chromosome 22 contains multiple segmental duplications (low-copy repeats) that confer a . . .

• Publisher: Massachusetts Medical Society
• Subject: Adaptor Proteins, Signal Transducing - genetics / Adolescent / Animals / Child / Chromosome 22 / Chromosome Deletion / Chromosomes / Chromosomes, Human, Pair 22 / Danio rerio / Defects / DiGeorge Syndrome - genetics / Embryos / Exome / Female / Gene deletion / Haploinsufficiency / Heterozygote / Humans / Infant / Infant, Newborn / Kidney - abnormalities / Kidneys / Life Sciences / Male / Mice / Models, Animal / Nervous system / Nonsense mutation / Nuclear Proteins - genetics / Phenotypes / Sequence Analysis, DNA / Thymic hypoplasia / Urinary tract / Urinary Tract - abnormalities / Urogenital system / Young Adult / Zebrafish