TY - CHAP
T1 - Mutational spectrum of the ctns gene in Egyptian patients with nephropathic cystinosis
AU - Soliman, Neveen A.
AU - Elmonem, Mohamed A.
AU - van den Heuvel, Lambertus
AU - Abdel Hamid, Rehab H.
AU - Gamal, Mohamed
AU - Bongaers, Inge
AU - Marie, Sandrine
AU - Levtchenko, Elena
N1 - Funding Information: We would like to thank our patients and their parents for their kind collaboration. This work was supported by a grant from the Cystinosis Research Network (CRN) to Neveen A Soliman and Elena Levtchenko in 2012. Elena Levtchenko was supported by the Fund for Scientific Research, Flanders (FWO. Vlaanderen), grant 1801110 N. Publisher Copyright: © 2014, SSIEM and Springer-Verlag Berlin Heidelberg.
PY - 2014
Y1 - 2014
N2 - Background: Nephropathic cystinosis is a rare autosomal recessive disorder caused by mutations in the CTNS gene, encoding for cystinosin, a carrier protein transporting cystine out of lysosomes. Its deficiency leads to cystine accumulation and cell damage in multiple organs, especially in the kidney. In this study, we aimed to provide the first report describing the mutational spectrum of Egyptian patients with nephropathic cystinosis and their genotype–phenotype correlation. Methods: Fifteen Egyptian patients from 13 unrelated families with infantile nephropathic cystinosis were evaluated clinically, biochemically, and genetically. Screening for the common 57-kb deletion was performed by standard multiplex PCR, followed by direct sequencing of the ten coding exons, exon-intron interfaces, and promoter region. Results: None of the 15 Egyptian patients had the 57-kb deletion. Twenty-seven mutant alleles and 12 pathogenic mutations were detected including six novel mutations: two frameshift (c.260_261delTT; p.F87SfsX36, c.1032delCinsTG; p.F345CfsX19), one nonsense (c.734G>A; p.W245fsX), two missense (c.1084G>A; pG362R, c.560A>G; p.K187R), and one intronic splicing mutation (IVS3+5g>t). A novel promoter region mutation (1-593-41C>T) seemed to be detected but was excluded as a pathogenic mutation by quantitative real-time PCR analysis. Conclusions: This study could be the basis for future genetic counseling and prenatal diagnosis of patients with nephropathic cystinosis in Egyptian and surrounding populations. The screening for the 57-kb deletion is not recommended anymore outside its geographical distribution, especially in the region of the Middle East. A common Middle Eastern mutation (c.681G>A; E227E) was pointed out and discussed.
AB - Background: Nephropathic cystinosis is a rare autosomal recessive disorder caused by mutations in the CTNS gene, encoding for cystinosin, a carrier protein transporting cystine out of lysosomes. Its deficiency leads to cystine accumulation and cell damage in multiple organs, especially in the kidney. In this study, we aimed to provide the first report describing the mutational spectrum of Egyptian patients with nephropathic cystinosis and their genotype–phenotype correlation. Methods: Fifteen Egyptian patients from 13 unrelated families with infantile nephropathic cystinosis were evaluated clinically, biochemically, and genetically. Screening for the common 57-kb deletion was performed by standard multiplex PCR, followed by direct sequencing of the ten coding exons, exon-intron interfaces, and promoter region. Results: None of the 15 Egyptian patients had the 57-kb deletion. Twenty-seven mutant alleles and 12 pathogenic mutations were detected including six novel mutations: two frameshift (c.260_261delTT; p.F87SfsX36, c.1032delCinsTG; p.F345CfsX19), one nonsense (c.734G>A; p.W245fsX), two missense (c.1084G>A; pG362R, c.560A>G; p.K187R), and one intronic splicing mutation (IVS3+5g>t). A novel promoter region mutation (1-593-41C>T) seemed to be detected but was excluded as a pathogenic mutation by quantitative real-time PCR analysis. Conclusions: This study could be the basis for future genetic counseling and prenatal diagnosis of patients with nephropathic cystinosis in Egyptian and surrounding populations. The screening for the 57-kb deletion is not recommended anymore outside its geographical distribution, especially in the region of the Middle East. A common Middle Eastern mutation (c.681G>A; E227E) was pointed out and discussed.
KW - Egyptian patient
KW - Inherited metabolic disorder
KW - Nephropathic cystinosis
KW - Renal fanconi syndrome
KW - Splice mutation
UR - http://www.scopus.com/inward/record.url?scp=85029878950&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/8904_2013_288
DO - https://doi.org/10.1007/8904_2013_288
M3 - Chapter
T3 - JIMD Reports
SP - 87
EP - 97
BT - JIMD Reports
PB - Springer
ER -