TITLE:
CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population
AUTHORS:
Filipa Ferreira, Inês Leal, David Sousa, Teresa Costa, Conceição Mota, Ana Marta Gomes, Daniela Lopes, Maria do Carmo Macário, Isabel Tavares, Helena Pinto, João Paulo Oliveira, Rita Magriço, Célia Carmona, Sónia Ramos, Raquel Neiva, Ana Marcão, Laura Vilarinho
KEYWORDS:
Cystinosis, CTNS Gene, Mutational Spectrum, Kidney Failure, 57-kb Deletion
JOURNAL NAME:
Open Journal of Genetics,
Vol.8 No.4,
December
28,
2018
ABSTRACT: Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal
membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese experience in the
diagnosis and management of patients with this rare disease over the past few
years and reports recurrent mutations in the CTNS gene. Methods:
Unrelated patients from different pediatric and adult hospitals all over
Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired
proximal reabsorption of amino acids, glycosuria and hypophosphatemia,
suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were
determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS, followed by direct sequencing of
the coding exons of CTNS. Results: From 1998 to 2017, twenty-one cystinotic patients were
biochemically diagnosed. From the remaining seventeen (four deceased), eleven
were studied for CTNS gene. Five out
of eleven patients were homozygous for the 57-kb deletion (10/22; 45.5%), and
other five were compound heterozygous for this variant (15/22; 68.2%). The other mutations found were p.Q128X (c.721 C>T;
2/22), p.S139F (c.755 C>T; 4/22) and c.18-21delGACT (p.T7FfsX7; 1/22). All
of these seventeen cystinotic patients are in treatment. Approximately 84% are
adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions:
The authors would like to emphasize the importance of first screening for the
57-kb deletion since it is very common in our population. This genetic study is
the first in our country and it could be the basis for future genetic
counseling in Portuguese population.