Medullary cystic kidney disease type 1: mutational analysis in 37 genes based on haplotype sharing

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Item Type:	Article
Title:	Medullary cystic kidney disease type 1: mutational analysis in 37 genes based on haplotype sharing
Creators Name:	Wolf, M.T., Mucha, B.E., Hennies, H.C., Attanasio, M., Panther, F., Zalewski, I., Karle, S.M., Otto, E.A., Deltas, C.C., Fuchshuber, A. and Hildebrandt, F.
Abstract:	Medullary cystic kidney disease type 1 (MCKD1) is an autosomal dominant, tubulo-interstitial nephropathy that causes renal salt wasting and end-stage renal failure in the fourth to seventh decade of life. MCKD1 was localized to chromosome 1q21. We demonstrated haplotype sharing and confirmed the telomeric border by a recombination of D1S2624 in a Belgian kindred. Since the causative gene has been elusive, high resolution haplotype analysis was performed in 16 kindreds. Clinical data and blood samples of 257 individuals (including 75 affected individuals) from 26 different kindreds were collected. Within the defined critical region mutational analysis of 37 genes (374 exons) in 23 MCKD1 patients was performed. In addition, for nine kindreds RT-PCR analysis for the sequenced genes was done to screen for mutations activating cryptic splice sites. We found consistency with the haplotype sharing hypothesis in an additional nine kindreds, detecting three different haplotype subsets shared within a region of 1.19 Mb. Mutational analysis of all 37 positional candidate genes revealed sequence variations in 3 different genes, AK000210, CCT3, and SCAMP3, that were segregating in each affected kindred and were not found in 96 healthy individuals, indicating, that a single responsible gene causing MCKD1 remains elusive. This may point to involvement of different genes within the MCKD1 critical region.
Keywords:	Chromosome Mapping, DNA Mutational Analysis, Haplotypes, Medullary Sponge Kidney, Microsatellite Repeats
Source:	Human Genetics
ISSN:	0340-6717
Publisher:	Springer
Volume:	119
Number:	6
Page Range:	649-658
Date:	July 2006
Official Publication:	https://doi.org/10.1007/s00439-006-0176-3
PubMed:	View item in PubMed

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