Further definition of the proximal 19p13.3 microdeletion/microduplication syndrome and implication of PIAS4 as the major contributor
| Autor: | Carlos A. Venegas-Vega, Irene Dapía, Juan C. Cigudosa, Sergio Ramos, María Calvente, Leandro Landera, Pedro Arias, Antonio González-Meneses, Luis A. Pérez-Jurado, Julián Nevado, Alicia Hernández, Jair Tenorio, Pablo Lapunzina |
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| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Male Microcephaly media_common.quotation_subject Developmental Disabilities Nonsense Locus (genetics) 030105 genetics & heredity 03 medical and health sciences Intellectual Disability Intellectual disability Chromosome Duplication Genetics Medicine Humans Abnormalities Multiple Child Poly-ADP-Ribose Binding Proteins Genetics (clinical) media_common Comparative Genomic Hybridization business.industry Macrocephaly medicine.disease Protein Inhibitors of Activated STAT Hypotonia Megalencephaly 030104 developmental biology Phenotype Speech delay dup Female medicine.symptom Chromosome Deletion business Chromosomes Human Pair 19 |
| Zdroj: | Clinical Genetics. 97(3):467-476 |
| ISSN: | 1399-0004 0009-9163 |
| DOI: | 10.1111/cge.13689 |
| Popis: | The proximal 19p13.3 microdeletion/microduplication (prox19p13.3del/dup) syndrome is a recently described disorder with common clinical features including developmental delay, intellectual disability, speech delay, facial dysmorphic features with ear defects, anomalies of the hands and feet, umbilical hernia and hypotonia. While deletions are associated with macrocephaly, patients with duplications have microcephaly. The smallest region of overlap in multiple patients (113.5 kb) included three genes and one pseudogene, with a suggested major role of PIAS4 in determination of the phenotype and head size in these patients. Here, we refine the prox19p13.3del/dup with four additional patients: two with microdeletions, one with microduplication and one family with single-nucleotide nonsense variant in PIAS4. The patient with the PIAS4 loss of function variant displayed a phenotype quite similar to deletion patients -including the macrocephaly and many other core features of the syndrome. Patient's SNV was inherited from her mother who is similarly affected. Thus, our data indicate that PIAS4 is a major contributor to the proximal 19p13.3del/dup syndrome phenotype. In summary, we report the first patient with a pathogenic variant in PIAS4- and three additional rearrangements at the proximal 19p13.3 locus. These observations add further evidence about the molecular basis of this microdeletion/microduplication syndrome. |
| Databáze: | OpenAIRE |
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