Abstract
Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering and identified 5 novel candidate genes (RBM48, FAM186B, PIAS1, INCENP, and RCOR1) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis, and allows identification of novel candidate genes.
| Original language | English |
|---|---|
| Pages (from-to) | 468-475 |
| Number of pages | 8 |
| Journal | Kidney International |
| Volume | 89 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2016 Feb 1 |
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All Science Journal Classification (ASJC) codes
- Nephrology
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Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity. / Braun, Daniela A.; Schueler, Markus; Halbritter, Jan; Gee, Heon Yung; Porath, Jonathan D.; Lawson, Jennifer A.; Airik, Rannar; Shril, Shirlee; Allen, Susan J.; Stein, Deborah; Al Kindy, Adila; Beck, Bodo B.; Cengiz, Nurcan; Moorani, Khemchand N.; Ozaltin, Fatih; Hashmi, Seema; Sayer, John A.; Bockenhauer, Detlef; Soliman, Neveen A.; Otto, Edgar A.; Lifton, Richard P.; Hildebrandt, Friedhelm.
In: Kidney International, Vol. 89, No. 2, 01.02.2016, p. 468-475.Research output: Contribution to journal › Article
TY - JOUR
T1 - Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity
AU - Braun, Daniela A.
AU - Schueler, Markus
AU - Halbritter, Jan
AU - Gee, Heon Yung
AU - Porath, Jonathan D.
AU - Lawson, Jennifer A.
AU - Airik, Rannar
AU - Shril, Shirlee
AU - Allen, Susan J.
AU - Stein, Deborah
AU - Al Kindy, Adila
AU - Beck, Bodo B.
AU - Cengiz, Nurcan
AU - Moorani, Khemchand N.
AU - Ozaltin, Fatih
AU - Hashmi, Seema
AU - Sayer, John A.
AU - Bockenhauer, Detlef
AU - Soliman, Neveen A.
AU - Otto, Edgar A.
AU - Lifton, Richard P.
AU - Hildebrandt, Friedhelm
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering and identified 5 novel candidate genes (RBM48, FAM186B, PIAS1, INCENP, and RCOR1) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis, and allows identification of novel candidate genes.
AB - Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering and identified 5 novel candidate genes (RBM48, FAM186B, PIAS1, INCENP, and RCOR1) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis, and allows identification of novel candidate genes.
UR - http://www.scopus.com/inward/record.url?scp=84944937498&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84944937498&partnerID=8YFLogxK
U2 - 10.1038/ki.2015.317
DO - 10.1038/ki.2015.317
M3 - Article
C2 - 26489029
AN - SCOPUS:84944937498
VL - 89
SP - 468
EP - 475
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 2
ER -