Universität zu Köln

Ebner, Kathrin, Dafinger, Claudia, Ortiz-Bruechle, Nadina, Koerber, Friederike, Schermer, Bernhard ORCID: 0000-0002-5194-9000, Benzing, Thomas, Doetsch, Joerg, Zerres, Klaus, Weber, Lutz Thorsten, Beck, Bodo B. and Liebau, Max Christoph ORCID: 0000-0003-0494-9080 (2017). Challenges in establishing genotype-phenotype correlations in ARPKD: case report on a toddler with two severe PKHD1 mutations. Pediatr. Nephrol., 32 (7). S. 1269 - 1274. NEW YORK: SPRINGER. ISSN 1432-198X

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Abstract

Autosomal recessive polycystic kidney disease (ARPKD) constitutes an important cause of pediatric end stage renal disease and is characterized by a broad phenotypic variability. The disease is caused by mutations in a single gene, Polycystic Kidney and Hepatic Disease 1 (PKHD1), which encodes a large transmembrane protein of poorly understood function called fibrocystin. Based on current knowledge of genotype-phenotype correlations in ARPKD, two truncating mutations are considered to result in a severe phenotype with peri- or neonatal mortality. Infants surviving the neonatal period are expected to carry at least one missense mutation. We report on a female patient with two truncating PKHD1 mutations who survived the first 30 months of life without renal replacement therapy. Our patient carries not only a known stop mutation, c.8011C > T (p.Arg2671*), but also the previously reported c.51A > G PKHD1 sequence variant of unknown significance in exon 2. Using functional in vitro studies we have confirmed the pathogenic nature of c.51A > G, demonstrating activation of a new donor splice site in intron 2 that results in a frameshift mutation and generation of a premature stop codon. This case illustrates the importance of functional mutation analyses and also raises questions regarding the current belief that the presence of at least one missense mutation is necessary for perinatal survival in ARPKD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ebner, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Dafinger, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Ortiz-Bruechle, Nadina UNSPECIFIED UNSPECIFIED UNSPECIFIED Koerber, Friederike UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED orcid.org/0000-0002-5194-9000 UNSPECIFIED Benzing, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Zerres, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Lutz Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Beck, Bodo B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Liebau, Max Christoph UNSPECIFIED orcid.org/0000-0003-0494-9080 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-226843
DOI:	10.1007/s00467-017-3648-x
Journal or Publication Title:	Pediatr. Nephrol.
Volume:	32
Number:	7
Page Range:	S. 1269 - 1274
Date:	2017
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-198X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POLYCYSTIC KIDNEY-DISEASE; TRANSCRIPTIONAL COMPLEXITY; GENE; SPECTRUM; PROTEIN; ENCODES Multiple languages Pediatrics; Urology & Nephrology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22684