Author(s)

Filipa Ferreira^1*, Inês Leal², David Sousa², Teresa Costa³, Conceição Mota³, Ana Marta Gomes⁴, Daniela Lopes⁴, Maria do Carmo Macário⁵, Isabel Tavares⁶, Helena Pinto⁶, João Paulo Oliveira^6,7,8, Rita Magriço⁹, Célia Carmona¹, Sónia Ramos¹, Raquel Neiva¹, Ana Marcão¹, Laura Vilarinho^1,10

¹Newborn Screening, Metabolism and Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.
²Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisboa, Portugal.
³Centro Hospitalar Universitário do Porto, Porto, Portugal.
⁴Centro Hospitalar Vila Nova de Gaia, Espinho, Portugal.
⁵Centro Hospitalar Universitário de Coimbra, CHUC, Coimbra, Portugal.
⁶Serviço de Genética Médica, Centro Hospitalar de São João, Porto, Portugal.
⁷Unidade de Genética, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
⁸I3S—Instituto de Investigação e Inovação em Saúde, Porto, Portugal.
⁹Serviço de Nefrologia do Hospital Garcia de Orta, Almada, Portugal.
¹⁰Research and Development Unit, Department of Human Genetics, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.

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.

Cystinosis, CTNS Gene, Mutational Spectrum, Kidney Failure, 57-kb Deletion

Ferreira, F. , Leal, I. , Sousa, D. , Costa, T. , Mota, C. , Gomes, A. , Lopes, D. , Carmo Macário, M. , Tavares, I. , Pinto, H. , Oliveira, J. , Magriço, R. , Carmona, C. , Ramos, S. , Neiva, R. , Marcão, A. and Vilarinho, L. (2018) CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population. Open Journal of Genetics, 8, 91-100. doi: 10.4236/ojgen.2018.84008.