Further definition of the proximal 19p13.3 microdeletion/microduplication syndrome and implication of PIAS4 as the major contributor
Por:
Tenorio, Jair, Nevado, Julian, Gonzalez-Meneses, Antonio, Arias, Pedro, Dapia, Irene, Venegas-Vega, Carlos A., Calvente, Maria, Hernandez, Alicia, Landera, Leandro, Ramos, Sergio, Cigudosa, Juan Cruz, Perez-Jurado, Luis A., Lapunzina, Pablo, SOGRI Consortium
Publicada:
1 mar 2020
Resumen:
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.
Filiaciones:
Tenorio, Jair:
Hosp Univ LaPaz UAM, Inst Genet Med & Mol INGEMM IdiPAZ, Madrid, Spain
ISCIII, CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Callede Melchor Fernandez Almagro, Madrid, Spain
ITHACA European Reference Network, ERN ITHACA, Brussels, Belgium
Nevado, Julian:
Hosp Univ LaPaz UAM, Inst Genet Med & Mol INGEMM IdiPAZ, Madrid, Spain
ISCIII, CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Callede Melchor Fernandez Almagro, Madrid, Spain
ITHACA European Reference Network, ERN ITHACA, Brussels, Belgium
Gonzalez-Meneses, Antonio:
Hosp Univ Virgen del Rocio, Dysmorphol & Metab Unit, Av Manuel Siurot, Seville, Spain
Arias, Pedro:
Hosp Univ LaPaz UAM, Inst Genet Med & Mol INGEMM IdiPAZ, Madrid, Spain
ISCIII, CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Callede Melchor Fernandez Almagro, Madrid, Spain
Dapia, Irene:
Hosp Univ LaPaz UAM, Inst Genet Med & Mol INGEMM IdiPAZ, Madrid, Spain
ISCIII, CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Callede Melchor Fernandez Almagro, Madrid, Spain
Venegas-Vega, Carlos A.:
Hosp Gen Mexico City, Unidad Genet, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Fac Med, Mexico City, DF, Mexico
Calvente, Maria:
NIMGENETICS, C Faraday 7,Parque Cient Madrid, Madrid, Spain
Hernandez, Alicia:
Hosp Univ LaPaz UAM, Inst Genet Med & Mol INGEMM IdiPAZ, Madrid, Spain
ISCIII, CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Callede Melchor Fernandez Almagro, Madrid, Spain
Landera, Leandro:
Univ Fed Rio de Janeiro, Congenital Malformat Lab, Ave Carlos Chagas Filho, Rio De Janeiro, Brazil
Ramos, Sergio:
Hosp Univ LaPaz UAM, Inst Genet Med & Mol INGEMM IdiPAZ, Madrid, Spain
ISCIII, CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Callede Melchor Fernandez Almagro, Madrid, Spain
Cigudosa, Juan Cruz:
NIMGENETICS, C Faraday 7,Parque Cient Madrid, Madrid, Spain
Perez-Jurado, Luis A.:
ISCIII, CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Callede Melchor Fernandez Almagro, Madrid, Spain
Univ Pompeu Fabra, Genet Unit, Barcelona, Spain
IMIM Hosp del Mar, Barcelona, Spain
Univ Adelaide, SAHMRI, Womens & Childrens Hosp, Adelaide, SA, Australia
Lapunzina, Pablo:
Hosp Univ LaPaz UAM, Inst Genet Med & Mol INGEMM IdiPAZ, Madrid, Spain
ISCIII, CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Callede Melchor Fernandez Almagro, Madrid, Spain
ITHACA European Reference Network, ERN ITHACA, Brussels, Belgium
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