Frontiers in Genetics (Jul 2021)
Deep Phenotyping and Genetic Characterization of a Cohort of 70 Individuals With 5p Minus Syndrome
- Julián Nevado,
- Julián Nevado,
- Julián Nevado,
- Cristina Bel-Fenellós,
- Ana Karen Sandoval-Talamantes,
- Ana Karen Sandoval-Talamantes,
- Ana Karen Sandoval-Talamantes,
- Ana Karen Sandoval-Talamantes,
- Ana Karen Sandoval-Talamantes,
- Adolfo Hernández,
- Chantal Biencinto-López,
- María Luisa Martínez-Fernández,
- Pilar Barrúz,
- Fernando Santos-Simarro,
- Fernando Santos-Simarro,
- Fernando Santos-Simarro,
- María Ángeles Mori-Álvarez,
- María Ángeles Mori-Álvarez,
- María Ángeles Mori-Álvarez,
- Elena Mansilla,
- Elena Mansilla,
- Elena Mansilla,
- Fé Amalia García-Santiago,
- Fé Amalia García-Santiago,
- Fé Amalia García-Santiago,
- Isabel Valcorba,
- Isabel Valcorba,
- Isabel Valcorba,
- Belén Sáenz-Rico,
- María Luisa Martínez-Frías,
- Pablo Lapunzina,
- Pablo Lapunzina,
- Pablo Lapunzina
Affiliations
- Julián Nevado
- CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos (ISCIII), Madrid, Spain
- Julián Nevado
- Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
- Julián Nevado
- ITHACA-European Reference Network-Hospital la Paz, Madrid, Spain
- Cristina Bel-Fenellós
- Departamento de Investigación y Psicología en Educación, Facultad de Educación, Universidad Complutense de Madrid (UCM), Madrid, Spain
- Ana Karen Sandoval-Talamantes
- CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos (ISCIII), Madrid, Spain
- Ana Karen Sandoval-Talamantes
- Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
- Ana Karen Sandoval-Talamantes
- ITHACA-European Reference Network-Hospital la Paz, Madrid, Spain
- Ana Karen Sandoval-Talamantes
- Departamento de Investigación y Psicología en Educación, Facultad de Educación, Universidad Complutense de Madrid (UCM), Madrid, Spain
- Ana Karen Sandoval-Talamantes
- Servicio de Genética, Centro de Rehabilitacion Infantil Teleton (CRIT), Guadalajara, Mexico
- Adolfo Hernández
- Departamento de Economía Financiera y Actuarial y Estadística, Facultad de Comercio y Turismo, Universidad Complutense de Madrid, Madrid, Spain
- Chantal Biencinto-López
- Departamento de Investigación y Psicología en Educación, Facultad de Educación, Universidad Complutense de Madrid (UCM), Madrid, Spain
- María Luisa Martínez-Fernández
- Spanish Collaborative Study of Congenital Malformations (ECEMC), Research Unit on Congenital Anomalies (UIAC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Pilar Barrúz
- CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos (ISCIII), Madrid, Spain
- Fernando Santos-Simarro
- CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos (ISCIII), Madrid, Spain
- Fernando Santos-Simarro
- Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
- Fernando Santos-Simarro
- ITHACA-European Reference Network-Hospital la Paz, Madrid, Spain
- María Ángeles Mori-Álvarez
- CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos (ISCIII), Madrid, Spain
- María Ángeles Mori-Álvarez
- Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
- María Ángeles Mori-Álvarez
- ITHACA-European Reference Network-Hospital la Paz, Madrid, Spain
- Elena Mansilla
- CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos (ISCIII), Madrid, Spain
- Elena Mansilla
- Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
- Elena Mansilla
- ITHACA-European Reference Network-Hospital la Paz, Madrid, Spain
- Fé Amalia García-Santiago
- CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos (ISCIII), Madrid, Spain
- Fé Amalia García-Santiago
- Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
- Fé Amalia García-Santiago
- ITHACA-European Reference Network-Hospital la Paz, Madrid, Spain
- Isabel Valcorba
- CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos (ISCIII), Madrid, Spain
- Isabel Valcorba
- Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
- Isabel Valcorba
- ITHACA-European Reference Network-Hospital la Paz, Madrid, Spain
- Belén Sáenz-Rico
- Departamento Estudios Educativos, Facultad de Educación, Universidad Complutense de Madrid, Madrid, Spain
- María Luisa Martínez-Frías
- Spanish Collaborative Study of Congenital Malformations (ECEMC), Research Unit on Congenital Anomalies (UIAC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Pablo Lapunzina
- CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos (ISCIII), Madrid, Spain
- Pablo Lapunzina
- Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain
- Pablo Lapunzina
- ITHACA-European Reference Network-Hospital la Paz, Madrid, Spain
- DOI
- https://doi.org/10.3389/fgene.2021.645595
- Journal volume & issue
-
Vol. 12
Abstract
Chromosome-5p minus syndrome (5p-Sd, OMIM #123450) formerly known as Cri du Chat syndrome results from the loss of genetic material at the distal region of the short arm of chromosome 5. It is a neurodevelopmental disorder of genetic cause. So far, about 400 patients have been reported worldwide. Individuals affected by this syndrome have large phenotypic heterogeneity. However, a specific phenotype has emerged including global developmental delay, microcephaly, delayed speech, some dysmorphic features, and a characteristic and monochromatic high-pitch voice, resembling a cat’s cry. We here describe a cohort of 70 patients with clinical features of 5p- Sd characterized by means of deep phenotyping, SNP arrays, and other genetic approaches. Individuals have a great clinical and molecular heterogeneity, which can be partially explained by the existence of additional significant genomic rearrangements in around 39% of cases. Thus, our data showed significant statistical differences between subpopulations (simple 5p deletions versus 5p deletions plus additional rearrangements) of the cohort. We also determined significant “functional” differences between male and female individuals.
Keywords