Whole-Exome Sequencing, Proteome Landscape, and Immune Cell Migration Patterns in a Clinical Context of Menkes Disease
Menkes disease (MD) is a rare and often lethal X-linked recessive syndrome, characterized by generalized alterations in copper transport and metabolism, linked to mutations in the ATPase copper transporting α (<i>ATP7A</i>) gene. Our objective was to identify genomic alterations and circ...
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MDPI AG
2021-05-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/5/744 |
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| author | Margarita L. Martinez-Fierro Griselda A. Cabral-Pacheco Idalia Garza-Veloz Jesus Acuña-Quiñones Laura E. Martinez-de-Villarreal Marisol Ibarra-Ramirez Joke Beuten Samantha E. Sanchez-Guerrero Laura Villarreal-Martinez Ivan Delgado-Enciso Iram P. Rodriguez-Sanchez Vania Z. Zuñiga-Ramirez Edith Cardenas-Vargas Viktor Romero-Diaz |
| author_facet | Margarita L. Martinez-Fierro Griselda A. Cabral-Pacheco Idalia Garza-Veloz Jesus Acuña-Quiñones Laura E. Martinez-de-Villarreal Marisol Ibarra-Ramirez Joke Beuten Samantha E. Sanchez-Guerrero Laura Villarreal-Martinez Ivan Delgado-Enciso Iram P. Rodriguez-Sanchez Vania Z. Zuñiga-Ramirez Edith Cardenas-Vargas Viktor Romero-Diaz |
| author_sort | Margarita L. Martinez-Fierro |
| collection | DOAJ |
| description | Menkes disease (MD) is a rare and often lethal X-linked recessive syndrome, characterized by generalized alterations in copper transport and metabolism, linked to mutations in the ATPase copper transporting α (<i>ATP7A</i>) gene. Our objective was to identify genomic alterations and circulating proteomic profiles related to MD assessing their potential roles in the clinical features of the disease. We describe the case of a male patient of 8 months of age with silvery hair, tan skin color, hypotonia, alterations in neurodevelopment, presence of seizures, and low values of plasma ceruloplasmin. Trio-whole-exome sequencing (Trio-WES) analysis, plasma proteome screening, and blood cell migration assays were carried out. Trio-WES revealed a hemizygous change c.4190C > T (p.S1397F) in exon 22 of the <i>ATP7A</i> gene. Compared with his parents and with child controls, 11 plasma proteins were upregulated and 59 downregulated in the patient. According to their biological processes, 42 (71.2%) of downregulated proteins had a participation in cellular transport. The immune system process was represented by 35 (59.3%) downregulated proteins (<i>p</i> = 9.44 × 10<sup>−11</sup>). Additional studies are necessary to validate these findings as hallmarks of MD. |
| first_indexed | 2024-03-10T11:23:59Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T11:23:59Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-79e66667716a4a91a205efe5fe1987cb2023-11-21T19:49:13ZengMDPI AGGenes2073-44252021-05-0112574410.3390/genes12050744Whole-Exome Sequencing, Proteome Landscape, and Immune Cell Migration Patterns in a Clinical Context of Menkes DiseaseMargarita L. Martinez-Fierro0Griselda A. Cabral-Pacheco1Idalia Garza-Veloz2Jesus Acuña-Quiñones3Laura E. Martinez-de-Villarreal4Marisol Ibarra-Ramirez5Joke Beuten6Samantha E. Sanchez-Guerrero7Laura Villarreal-Martinez8Ivan Delgado-Enciso9Iram P. Rodriguez-Sanchez10Vania Z. Zuñiga-Ramirez11Edith Cardenas-Vargas12Viktor Romero-Diaz13Molecular Medicine Laboratory, Unidad Académica de Medicina Humana y C.S, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6, Ejido la Escondida, Zacatecas 98160, MexicoMolecular Medicine Laboratory, Unidad Académica de Medicina Humana y C.S, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6, Ejido la Escondida, Zacatecas 98160, MexicoMolecular Medicine Laboratory, Unidad Académica de Medicina Humana y C.S, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6, Ejido la Escondida, Zacatecas 98160, MexicoMolecular Medicine Laboratory, Unidad Académica de Medicina Humana y C.S, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6, Ejido la Escondida, Zacatecas 98160, MexicoDepartamento de Genética, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey 64460, MexicoDepartamento de Genética, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey 64460, MexicoAiLife Diagnostics, 1920 Country Pl Pkwy Suite 100, Pearland, TX 77584, USAHospital General Zacatecas “Luz González Cosío”, Servicios de Salud de Zacatecas, Zacatecas 98160, MexicoHematology Service, Hospital Universitario “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo León, Monterrey 64460, MexicoDepartment of Molecular Medicine, School of Medicine, University of Colima, Colima 28040, MexicoMolecular and Structural Physiology Laboratory, School of Biological Sciences, Autonomous University of Nuevo León, Monterrey 64460, MexicoMolecular Medicine Laboratory, Unidad Académica de Medicina Humana y C.S, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6, Ejido la Escondida, Zacatecas 98160, MexicoHospital General Zacatecas “Luz González Cosío”, Servicios de Salud de Zacatecas, Zacatecas 98160, MexicoDepartment of Histology, Universidad Autónoma de Nuevo León, Facultad de Medicina, Monterrey 64460, MexicoMenkes disease (MD) is a rare and often lethal X-linked recessive syndrome, characterized by generalized alterations in copper transport and metabolism, linked to mutations in the ATPase copper transporting α (<i>ATP7A</i>) gene. Our objective was to identify genomic alterations and circulating proteomic profiles related to MD assessing their potential roles in the clinical features of the disease. We describe the case of a male patient of 8 months of age with silvery hair, tan skin color, hypotonia, alterations in neurodevelopment, presence of seizures, and low values of plasma ceruloplasmin. Trio-whole-exome sequencing (Trio-WES) analysis, plasma proteome screening, and blood cell migration assays were carried out. Trio-WES revealed a hemizygous change c.4190C > T (p.S1397F) in exon 22 of the <i>ATP7A</i> gene. Compared with his parents and with child controls, 11 plasma proteins were upregulated and 59 downregulated in the patient. According to their biological processes, 42 (71.2%) of downregulated proteins had a participation in cellular transport. The immune system process was represented by 35 (59.3%) downregulated proteins (<i>p</i> = 9.44 × 10<sup>−11</sup>). Additional studies are necessary to validate these findings as hallmarks of MD.https://www.mdpi.com/2073-4425/12/5/744Menkes diseasesilvery hair syndromerare diseaseexome sequencinghypopigmentary disorder |
| spellingShingle | Margarita L. Martinez-Fierro Griselda A. Cabral-Pacheco Idalia Garza-Veloz Jesus Acuña-Quiñones Laura E. Martinez-de-Villarreal Marisol Ibarra-Ramirez Joke Beuten Samantha E. Sanchez-Guerrero Laura Villarreal-Martinez Ivan Delgado-Enciso Iram P. Rodriguez-Sanchez Vania Z. Zuñiga-Ramirez Edith Cardenas-Vargas Viktor Romero-Diaz Whole-Exome Sequencing, Proteome Landscape, and Immune Cell Migration Patterns in a Clinical Context of Menkes Disease Genes Menkes disease silvery hair syndrome rare disease exome sequencing hypopigmentary disorder |
| title | Whole-Exome Sequencing, Proteome Landscape, and Immune Cell Migration Patterns in a Clinical Context of Menkes Disease |
| title_full | Whole-Exome Sequencing, Proteome Landscape, and Immune Cell Migration Patterns in a Clinical Context of Menkes Disease |
| title_fullStr | Whole-Exome Sequencing, Proteome Landscape, and Immune Cell Migration Patterns in a Clinical Context of Menkes Disease |
| title_full_unstemmed | Whole-Exome Sequencing, Proteome Landscape, and Immune Cell Migration Patterns in a Clinical Context of Menkes Disease |
| title_short | Whole-Exome Sequencing, Proteome Landscape, and Immune Cell Migration Patterns in a Clinical Context of Menkes Disease |
| title_sort | whole exome sequencing proteome landscape and immune cell migration patterns in a clinical context of menkes disease |
| topic | Menkes disease silvery hair syndrome rare disease exome sequencing hypopigmentary disorder |
| url | https://www.mdpi.com/2073-4425/12/5/744 |
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