Publication
Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients
| Summary: | Cystinuria is a rare autosomal inherited disorder characterized by impaired transport of cystine and dibasic aminoacids in the proximal renal tubule. Classically, cystinuria is classified as type I (silent heterozygotes) and non-type I (heterozygotes with urinary hyperexcretion of cystine). Molecularly, cystinuria is classified as type A (mutations on SLC3A1 gene) and type B (mutations on SLC7A9 gene). The goal of this study is to provide a comprehensive clinical, biochemical and molecular characterization of a cohort of 12 Portuguese patients affected with cystinuria in order to provide insight into genotype-phenotype correlations. We describe seven type I and five non-type I patients. Regarding the molecular classification, seven patients were type A and five were type B. In SLC3A1 gene, two large genomic rearrangements and 13 sequence variants, including four new variants c.611-2A>C; c.1136+44G>A; c.1597T (p.Y533N); c.*70A>G, were found. One large genomic rearrangement was found in SLC7A9 gene as well as 24 sequence variants including 3 novel variants: c.216C>T (p.C72C), c.1119G>A (p.S373S) and c.*82C>T. In our cohort the most frequent pathogenic mutations were: large rearrangements (33.3% of mutant alleles) and a missense mutation c.1400T>C (p.M467T) (11.1%). This report expands the spectrum of SLC3A1 and SLC7A9 mutations and provides guidance in the clinical implementation of molecular assays in routine genetic counseling of Portuguese patients affected with cystinuria. |
|---|---|
| Main Authors: | Barbosa, Mafalda Fernanda Cabral Santos |
| Other Authors: | Lopes, A.; Mota, C.; Martins, E.; Oliveira, J.; Alves, S.; Bonis, P. de; Mota, M. do Céu; Dias, C.; Santos, P. Rodrigues; Fortuna, A. M.; Quelhas, D.; Lacerda, L.; Biscegliah, L.; Cardoso, M. L. |
| Subject: | Cystinuria MLPA analysis silent mutation SLC3A1 gene SLC7A9 gene |
| Year: | 2012 |
| Country: | Portugal |
| Document type: | article |
| Access type: | restricted access |
| Associated institution: | Universidade do Minho |
| Language: | English |
| Origin: | RepositóriUM - Universidade do Minho |
| _version_ | 1867438544982638592 |
|---|---|
| author | Barbosa, Mafalda Fernanda Cabral Santos |
| author2 | Lopes, A. Mota, C. Martins, E. Oliveira, J. Alves, S. Bonis, P. de Mota, M. do Céu Dias, C. Santos, P. Rodrigues Fortuna, A. M. Quelhas, D. Lacerda, L. Biscegliah, L. Cardoso, M. L. |
| author2_role | author author author author author author author author author author author author author author |
| author_facet | Barbosa, Mafalda Fernanda Cabral Santos Lopes, A. Mota, C. Martins, E. Oliveira, J. Alves, S. Bonis, P. de Mota, M. do Céu Dias, C. Santos, P. Rodrigues Fortuna, A. M. Quelhas, D. Lacerda, L. Biscegliah, L. Cardoso, M. L. |
| author_role | author |
| contributor_name_str_mv | RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Barbosa, Mafalda Fernanda Cabral Santos\"},{\"Person.name\":\"Lopes, A.\"},{\"Person.name\":\"Mota, C.\"},{\"Person.name\":\"Martins, E.\"},{\"Person.name\":\"Oliveira, J.\"},{\"Person.name\":\"Alves, S.\"},{\"Person.name\":\"Bonis, P. de\"},{\"Person.name\":\"Mota, M. do Céu\"},{\"Person.name\":\"Dias, C.\"},{\"Person.name\":\"Santos, P. Rodrigues\"},{\"Person.name\":\"Fortuna, A. M.\"},{\"Person.name\":\"Quelhas, D.\"},{\"Person.name\":\"Lacerda, L.\"},{\"Person.name\":\"Biscegliah, L.\"},{\"Person.name\":\"Cardoso, M. L.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Barbosa, Mafalda Fernanda Cabral Santos Lopes, A. Mota, C. Martins, E. Oliveira, J. Alves, S. Bonis, P. de Mota, M. do Céu Dias, C. Santos, P. Rodrigues Fortuna, A. M. Quelhas, D. Lacerda, L. Biscegliah, L. Cardoso, M. L. |
| datacite.date.Accepted.fl_str_mv | 2012-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2015-02-05T12:07:21Z |
| datacite.date.embargoed.fl_str_mv | 2015-02-05T12:07:21Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| datacite.subjects.subject.fl_str_mv | Cystinuria MLPA analysis silent mutation SLC3A1 gene SLC7A9 gene |
| datacite.titles.title.fl_str_mv | Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients |
| dc.contributor.none.fl_str_mv | RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | Barbosa, Mafalda Fernanda Cabral Santos Lopes, A. Mota, C. Martins, E. Oliveira, J. Alves, S. Bonis, P. de Mota, M. do Céu Dias, C. Santos, P. Rodrigues Fortuna, A. M. Quelhas, D. Lacerda, L. Biscegliah, L. Cardoso, M. L. |
| dc.date.Accepted.fl_str_mv | 2012-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2015-02-05T12:07:21Z |
| dc.date.embargoed.fl_str_mv | 2015-02-05T12:07:21Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/33600 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | John Wiley and Sons |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| dc.subject.none.fl_str_mv | Cystinuria MLPA analysis silent mutation SLC3A1 gene SLC7A9 gene |
| dc.title.fl_str_mv | Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Cystinuria is a rare autosomal inherited disorder characterized by impaired transport of cystine and dibasic aminoacids in the proximal renal tubule. Classically, cystinuria is classified as type I (silent heterozygotes) and non-type I (heterozygotes with urinary hyperexcretion of cystine). Molecularly, cystinuria is classified as type A (mutations on SLC3A1 gene) and type B (mutations on SLC7A9 gene). The goal of this study is to provide a comprehensive clinical, biochemical and molecular characterization of a cohort of 12 Portuguese patients affected with cystinuria in order to provide insight into genotype-phenotype correlations. We describe seven type I and five non-type I patients. Regarding the molecular classification, seven patients were type A and five were type B. In SLC3A1 gene, two large genomic rearrangements and 13 sequence variants, including four new variants c.611-2A>C; c.1136+44G>A; c.1597T (p.Y533N); c.*70A>G, were found. One large genomic rearrangement was found in SLC7A9 gene as well as 24 sequence variants including 3 novel variants: c.216C>T (p.C72C), c.1119G>A (p.S373S) and c.*82C>T. In our cohort the most frequent pathogenic mutations were: large rearrangements (33.3% of mutant alleles) and a missense mutation c.1400T>C (p.M467T) (11.1%). This report expands the spectrum of SLC3A1 and SLC7A9 mutations and provides guidance in the clinical implementation of molecular assays in routine genetic counseling of Portuguese patients affected with cystinuria. |
| dirty | 0 |
| eu_rights_str_mv | restrictedAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/ac1986d4-8218-471d-b71b-31a097f7c388/download |
| id | rum_480620a163bea4abd4d20e8a2fd4e070 |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/33600 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/33600 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Barbosa, Mafalda Fernanda Cabral Santos Lopes, A. Mota, C. Martins, E. Oliveira, J. Alves, S. Bonis, P. de Mota, M. do Céu Dias, C. Santos, P. Rodrigues Fortuna, A. M. Quelhas, D. Lacerda, L. Biscegliah, L. Cardoso, M. L. |
| publishDate | 2012 |
| publisher.none.fl_str_mv | John Wiley and Sons |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engJohn Wiley and SonsporCystinuria is a rare autosomal inherited disorder characterized by impaired transport of cystine and dibasic aminoacids in the proximal renal tubule. Classically, cystinuria is classified as type I (silent heterozygotes) and non-type I (heterozygotes with urinary hyperexcretion of cystine). Molecularly, cystinuria is classified as type A (mutations on SLC3A1 gene) and type B (mutations on SLC7A9 gene). The goal of this study is to provide a comprehensive clinical, biochemical and molecular characterization of a cohort of 12 Portuguese patients affected with cystinuria in order to provide insight into genotype-phenotype correlations. We describe seven type I and five non-type I patients. Regarding the molecular classification, seven patients were type A and five were type B. In SLC3A1 gene, two large genomic rearrangements and 13 sequence variants, including four new variants c.611-2A>C; c.1136+44G>A; c.1597T (p.Y533N); c.*70A>G, were found. One large genomic rearrangement was found in SLC7A9 gene as well as 24 sequence variants including 3 novel variants: c.216C>T (p.C72C), c.1119G>A (p.S373S) and c.*82C>T. In our cohort the most frequent pathogenic mutations were: large rearrangements (33.3% of mutant alleles) and a missense mutation c.1400T>C (p.M467T) (11.1%). This report expands the spectrum of SLC3A1 and SLC7A9 mutations and provides guidance in the clinical implementation of molecular assays in routine genetic counseling of Portuguese patients affected with cystinuria.application/pdfporClinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patientsBarbosa, Mafalda Fernanda Cabral SantosLopes, A.Mota, C.Martins, E.Oliveira, J.Alves, S.Bonis, P. deMota, M. do CéuDias, C.Santos, P. RodriguesFortuna, A. M.Quelhas, D.Lacerda, L.Biscegliah, L.Cardoso, M. L.HostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptPMID21255007ISSNIsPartOf0009-9163DOIIsPartOf10.1111/j.1399-0004.2011.01638.x2015-02-05T12:07:21Z20122015-01-30T16:25:53Z2012-01-01T00:00:00ZHandlehttps://hdl.handle.net/1822/33600http://purl.org/coar/access_right/c_16ecrestricted accessCystinuriaMLPA analysissilent mutationSLC3A1 geneSLC7A9 gene581016 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://repositorium.uminho.pt/bitstreams/ac1986d4-8218-471d-b71b-31a097f7c388/download |
| spellingShingle | Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients Barbosa, Mafalda Fernanda Cabral Santos Cystinuria MLPA analysis silent mutation SLC3A1 gene SLC7A9 gene |
| status | SINGLETON |
| subject.fl_str_mv | Cystinuria MLPA analysis silent mutation SLC3A1 gene SLC7A9 gene |
| title | Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients |
| title_full | Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients |
| title_fullStr | Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients |
| title_full_unstemmed | Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients |
| title_short | Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients |
| title_sort | Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients |
| topic | Cystinuria MLPA analysis silent mutation SLC3A1 gene SLC7A9 gene |
| topic_facet | Cystinuria MLPA analysis silent mutation SLC3A1 gene SLC7A9 gene |
| url | https://hdl.handle.net/1822/33600 |
| visible | 1 |