TY - JOUR
T1 - PHF21A Related Disorder
T2 - Description of a New Case
AU - Butera, Ambra
AU - Nicotera, Antonio Gennaro
AU - Di Rosa, Gabriella
AU - Musumeci, Sebastiano Antonino
AU - Vitello, Girolamo Aurelio
AU - Musumeci, Antonino
AU - Vinci, Mirella
AU - Gloria, Angelo
AU - Federico, Concetta
AU - Saccone, Salvatore
AU - Calì, Francesco
N1 - Funding Information:
This work has been partially supported by the Italian Ministry of Health—“Ricerca Corrente” and 5 x mille”, and by Research Plan PIACERI L.3 Starting Grant from Dept. Biological, Geological and Environmental Sciences, University of Catania, to C.F.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/12
Y1 - 2022/12
N2 - PHF21A (PHD finger protein 21A) gene, located in the short arm of chromosome 11, encodes for BHC80, a component of the Lysine Specific Demethylase 1, Corepressor of REST (LSD1-CoREST) complex. BHC80 is mainly expressed in the human fetal brain and skeletal muscle and acts as a modulator of several neuronal genes during embryogenesis. Data from literature relates PHF21A variants with Potocki–Shaffer Syndrome (PSS), a contiguous gene deletion disorder caused by the haploinsufficiency of PHF21A, ALX4, and EXT2 genes. Clinical cardinal features of PSS syndrome are multiple exostoses (due to the EXT2 involvement), biparietal foramina (due to the ALX4 involvement), intellectual disability, and craniofacial anomalies (due to the PHF21A involvement). To date, to the best of our knowledge, a detailed description of PHF21A-related disorder clinical phenotype is not described in the literature; in fact, only 14 subjects with microdeletion frameshift or nonsense variants concerning only PHF21A gene have been reported. All reported cases did not present ALX4 or EXT2 variants, and their clinical features did not fit with PSS diagnosis. Herein, by using Exome sequencing, and Sanger sequencing of the region of interest, we describe a case of a child with a paternally inherited (mosaicism of 5%) truncating variant of the PHF21A gene (c.649_650del; p.Gln217ValfsTer6), and discuss the new evidence. In conclusion, these patients showed varied clinical expressions, mainly including the presence of intellectual disability, epilepsy, hypotonia, and dysmorphic features. Our study contributes to describing the genotype–phenotype spectrum of patients with PHF21A-related disorder; however, the limited data in the literature have been unable to provide a precise diagnostic protocol for patients with PHF21A-related disorder.
AB - PHF21A (PHD finger protein 21A) gene, located in the short arm of chromosome 11, encodes for BHC80, a component of the Lysine Specific Demethylase 1, Corepressor of REST (LSD1-CoREST) complex. BHC80 is mainly expressed in the human fetal brain and skeletal muscle and acts as a modulator of several neuronal genes during embryogenesis. Data from literature relates PHF21A variants with Potocki–Shaffer Syndrome (PSS), a contiguous gene deletion disorder caused by the haploinsufficiency of PHF21A, ALX4, and EXT2 genes. Clinical cardinal features of PSS syndrome are multiple exostoses (due to the EXT2 involvement), biparietal foramina (due to the ALX4 involvement), intellectual disability, and craniofacial anomalies (due to the PHF21A involvement). To date, to the best of our knowledge, a detailed description of PHF21A-related disorder clinical phenotype is not described in the literature; in fact, only 14 subjects with microdeletion frameshift or nonsense variants concerning only PHF21A gene have been reported. All reported cases did not present ALX4 or EXT2 variants, and their clinical features did not fit with PSS diagnosis. Herein, by using Exome sequencing, and Sanger sequencing of the region of interest, we describe a case of a child with a paternally inherited (mosaicism of 5%) truncating variant of the PHF21A gene (c.649_650del; p.Gln217ValfsTer6), and discuss the new evidence. In conclusion, these patients showed varied clinical expressions, mainly including the presence of intellectual disability, epilepsy, hypotonia, and dysmorphic features. Our study contributes to describing the genotype–phenotype spectrum of patients with PHF21A-related disorder; however, the limited data in the literature have been unable to provide a precise diagnostic protocol for patients with PHF21A-related disorder.
KW - BHC80
KW - contiguous gene deletion
KW - human chromosome 11
KW - hypotonia
KW - intellectual disability
KW - PHF21A gene
KW - Potocki–Shaffer syndrome
UR - http://www.scopus.com/inward/record.url?scp=85144517855&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85144517855&partnerID=8YFLogxK
U2 - 10.3390/ijms232416130
DO - 10.3390/ijms232416130
M3 - Article
C2 - 36555772
AN - SCOPUS:85144517855
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 24
M1 - 16130
ER -