Genetic and clinical characterization of 73 Pigmentary Mosaicism patients: revealing the genetic basis of clinical manifestations
Abstract Background Pigmentary mosaicism constitutes a heterogeneous group of skin pigmentation alterations associated with multisystem involvement. The aim of this study was to establish a complete cytogenetic and molecular characterization of PM patients, emphasizing on searching for possible low...
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| Language: | English |
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BMC
2019-11-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-019-1208-0 |
| _version_ | 1811295287673618432 |
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| author | C. Salas-Labadía S. Gómez-Carmona R. Cruz-Alcívar D. Martínez-Anaya V. Del Castillo-Ruiz C. Durán-McKinster V. Ulloa-Avilés E. Yokoyama-Rebollar A. Ruiz-Herrera P. Navarrete-Meneses E. Lieberman-Hernández A. González-Del Angel D. Cervantes-Barragán C. Villarroel-Cortés A. Reyes-León D. Suárez-Pérez A. Pedraza-Meléndez A. González-Orsuna P. Pérez-Vera |
| author_facet | C. Salas-Labadía S. Gómez-Carmona R. Cruz-Alcívar D. Martínez-Anaya V. Del Castillo-Ruiz C. Durán-McKinster V. Ulloa-Avilés E. Yokoyama-Rebollar A. Ruiz-Herrera P. Navarrete-Meneses E. Lieberman-Hernández A. González-Del Angel D. Cervantes-Barragán C. Villarroel-Cortés A. Reyes-León D. Suárez-Pérez A. Pedraza-Meléndez A. González-Orsuna P. Pérez-Vera |
| author_sort | C. Salas-Labadía |
| collection | DOAJ |
| description | Abstract Background Pigmentary mosaicism constitutes a heterogeneous group of skin pigmentation alterations associated with multisystem involvement. The aim of this study was to establish a complete cytogenetic and molecular characterization of PM patients, emphasizing on searching for possible low chromosomal mosaicism and on establishing an accurate genotype-phenotype correlation. Results A total of 73 patients were included (3 months to 18 years of age), 52% male and 48% female. Observed in 69 (95%) patients, the most frequent pattern of pigmentation was fine and whorled BL, which was associated with disseminated skin extent in 41 (59%) patients. Central nervous system (84%) alterations were the most frequent observed in the group of patients, followed by the musculoskeletal (53%) and ophthalmologic (27%) alterations. Considering the pattern of pigmentation, no significant differences in association with skin extent or extracutaneous manifestations were detected. Following a strict cytogenetic analysis strategy, screening metaphases from three different tissues (peripheral blood, hyperpigmented and hypopigmented skin) we found that 23/73 patients had chromosomal abnormalities classified as follows: 1) Mosaic with 2 or more different cell lines with structural alterations n = 19; 2) Polyploidy (mosaic) n = 1 and 3) Alterations in all cells in three different tissues n = 3. SNP array, array CGH and FISH were useful for the complete characterization of the chromosomal aberrations, for the detection of microdeletions in patients with normal karyotype but with strong clinical suspicious of chromosomal alteration, and for a better establishment of genotype-phenotype correlation. In 2 patients we found genes associated with some of the extracutaneous manifestations (SHH, MNX1, PPP2R2C). Conclusions This group of 73 patients finely described is the largest series of patients with pigmentary mosaicism reported worldwide. As we showed in this study, the followed analysis strategy allowed the detection of cytogenetic and molecular abnormalities, and made possible the establishment of genotype-phenotype associations in some patients. An important limitation of our study was the analysis of fibroblasts cultures instead of melanocytes and keratinocytes. In some cases the direct molecular DNA analysis of skin biopsy could be another choice. |
| first_indexed | 2024-04-13T05:30:03Z |
| format | Article |
| id | doaj.art-3f654e9d49a44d4795a0f54cee82e329 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-13T05:30:03Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-3f654e9d49a44d4795a0f54cee82e3292022-12-22T03:00:27ZengBMCOrphanet Journal of Rare Diseases1750-11722019-11-0114111110.1186/s13023-019-1208-0Genetic and clinical characterization of 73 Pigmentary Mosaicism patients: revealing the genetic basis of clinical manifestationsC. Salas-Labadía0S. Gómez-Carmona1R. Cruz-Alcívar2D. Martínez-Anaya3V. Del Castillo-Ruiz4C. Durán-McKinster5V. Ulloa-Avilés6E. Yokoyama-Rebollar7A. Ruiz-Herrera8P. Navarrete-Meneses9E. Lieberman-Hernández10A. González-Del Angel11D. Cervantes-Barragán12C. Villarroel-Cortés13A. Reyes-León14D. Suárez-Pérez15A. Pedraza-Meléndez16A. González-Orsuna17P. Pérez-Vera18Laboratorio de Genética y Cáncer, Departamento de Genética Humana, Instituto Nacional de PediatríaDepartamento de Genética Médica, Centro de Rehabilitación e Inclusión Infantil TeletónLaboratorio de Genética y Cáncer, Departamento de Genética Humana, Instituto Nacional de PediatríaLaboratorio de Genética y Cáncer, Departamento de Genética Humana, Instituto Nacional de PediatríaDepartamento de Genética Humana, Instituto Nacional de PediatríaDepartamento de Dermatología, Instituto Nacional de PediatríaLaboratorio de Genética y Cáncer, Departamento de Genética Humana, Instituto Nacional de PediatríaDepartamento de Genética Humana, Instituto Nacional de PediatríaHospital de Especialidades Pediátrico de LeónLaboratorio de Genética y Cáncer, Departamento de Genética Humana, Instituto Nacional de PediatríaDepartamento de Genética Humana, Instituto Nacional de PediatríaLaboratorio de Biología Molecular, Departamento de Genética Humana, Instituto Nacional de PediatríaHospital Central Sur de Alta Especialidad, PEMEXDepartamento de Genética Humana, Instituto Nacional de PediatríaLaboratorio de Genética y Cáncer, Departamento de Genética Humana, Instituto Nacional de PediatríaDepartamento de Genética Humana, Instituto Nacional de PediatríaLaboratorio de Genética y Cáncer, Departamento de Genética Humana, Instituto Nacional de PediatríaLaboratorio de Genética y Cáncer, Departamento de Genética Humana, Instituto Nacional de PediatríaLaboratorio de Genética y Cáncer, Departamento de Genética Humana, Instituto Nacional de PediatríaAbstract Background Pigmentary mosaicism constitutes a heterogeneous group of skin pigmentation alterations associated with multisystem involvement. The aim of this study was to establish a complete cytogenetic and molecular characterization of PM patients, emphasizing on searching for possible low chromosomal mosaicism and on establishing an accurate genotype-phenotype correlation. Results A total of 73 patients were included (3 months to 18 years of age), 52% male and 48% female. Observed in 69 (95%) patients, the most frequent pattern of pigmentation was fine and whorled BL, which was associated with disseminated skin extent in 41 (59%) patients. Central nervous system (84%) alterations were the most frequent observed in the group of patients, followed by the musculoskeletal (53%) and ophthalmologic (27%) alterations. Considering the pattern of pigmentation, no significant differences in association with skin extent or extracutaneous manifestations were detected. Following a strict cytogenetic analysis strategy, screening metaphases from three different tissues (peripheral blood, hyperpigmented and hypopigmented skin) we found that 23/73 patients had chromosomal abnormalities classified as follows: 1) Mosaic with 2 or more different cell lines with structural alterations n = 19; 2) Polyploidy (mosaic) n = 1 and 3) Alterations in all cells in three different tissues n = 3. SNP array, array CGH and FISH were useful for the complete characterization of the chromosomal aberrations, for the detection of microdeletions in patients with normal karyotype but with strong clinical suspicious of chromosomal alteration, and for a better establishment of genotype-phenotype correlation. In 2 patients we found genes associated with some of the extracutaneous manifestations (SHH, MNX1, PPP2R2C). Conclusions This group of 73 patients finely described is the largest series of patients with pigmentary mosaicism reported worldwide. As we showed in this study, the followed analysis strategy allowed the detection of cytogenetic and molecular abnormalities, and made possible the establishment of genotype-phenotype associations in some patients. An important limitation of our study was the analysis of fibroblasts cultures instead of melanocytes and keratinocytes. In some cases the direct molecular DNA analysis of skin biopsy could be another choice.http://link.springer.com/article/10.1186/s13023-019-1208-0Pigmentary mosaicismCytogenetic and molecular characterizationGenotype-phenotype correlation |
| spellingShingle | C. Salas-Labadía S. Gómez-Carmona R. Cruz-Alcívar D. Martínez-Anaya V. Del Castillo-Ruiz C. Durán-McKinster V. Ulloa-Avilés E. Yokoyama-Rebollar A. Ruiz-Herrera P. Navarrete-Meneses E. Lieberman-Hernández A. González-Del Angel D. Cervantes-Barragán C. Villarroel-Cortés A. Reyes-León D. Suárez-Pérez A. Pedraza-Meléndez A. González-Orsuna P. Pérez-Vera Genetic and clinical characterization of 73 Pigmentary Mosaicism patients: revealing the genetic basis of clinical manifestations Orphanet Journal of Rare Diseases Pigmentary mosaicism Cytogenetic and molecular characterization Genotype-phenotype correlation |
| title | Genetic and clinical characterization of 73 Pigmentary Mosaicism patients: revealing the genetic basis of clinical manifestations |
| title_full | Genetic and clinical characterization of 73 Pigmentary Mosaicism patients: revealing the genetic basis of clinical manifestations |
| title_fullStr | Genetic and clinical characterization of 73 Pigmentary Mosaicism patients: revealing the genetic basis of clinical manifestations |
| title_full_unstemmed | Genetic and clinical characterization of 73 Pigmentary Mosaicism patients: revealing the genetic basis of clinical manifestations |
| title_short | Genetic and clinical characterization of 73 Pigmentary Mosaicism patients: revealing the genetic basis of clinical manifestations |
| title_sort | genetic and clinical characterization of 73 pigmentary mosaicism patients revealing the genetic basis of clinical manifestations |
| topic | Pigmentary mosaicism Cytogenetic and molecular characterization Genotype-phenotype correlation |
| url | http://link.springer.com/article/10.1186/s13023-019-1208-0 |
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