Expanding the phenotype of PIGP deficiency to multiple congenital anomalies-hypotonia-seizures syndrome

Autores de IIS La Fe

• Carla Martín Grau

  Autor

• Carmen Orellana Alonso

  Autor

• Roberto Llorens Salvador

  Autor

• Purificación Marín Reina

  Autor

• 

  Francisco Martínez Castellano

  Autor

Participantes ajenos a IIS La Fe

• Rosello Piera, Monica
• Pedrola Vidal, Laia
• Quiroga, Ramiro
• Rubio Moll, Juan Salvador
• Gomez Portero, Rosa

Grupos

• Investigacion Biomédica en Imagen (GIBI 2-30)

  Investigador Principal

  Leonor Cerdá Alberich

• Investigación Traslacional en Genética

  

  Leader

  Francisco Martínez Castellano

Abstract

Glycosylphosphatidylinositol-anchored proteins are involved in multiple physiological processes and the initial stage of their biosynthesis is mediated by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY, and DMP2 genes, which have been linked to a wide spectrum of phenotypes depending on the gene damaged. To date, the PIGP gene has only been related to Developmental and Epileptic Encephalopathy 55 (MIM#617599) in just seven patients. A detailed medical history was performed in two affected siblings with a multiple malformation syndrome. Genetic testing was performed using whole-exome sequencing. One patient presented dysmorphic features, congenital anomalies, hypotonia and epileptic encephalopathy as described in PIGA, PIGQ and PIGY deficiencies. The other one was a fetus with a severe malformation disorder at 17 weeks of gestation whose pregnancy was interrupted. Both were compound heterozygous of pathogenic variants in PIGP gene: NM_153682.3:c.2 T > C(p.?) and a 136 Kb deletion (GRCh37/hg19 21q22.13(chr21:38329939-38 466 066)x1) affecting the entire PIGP gene. Our results extend the clinical phenotype associated to PIGP gene and propose to include it as a novel cause of Multiple Congenital Anomalies-Hypotonia-Seizures syndrome.

© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Keywords

• PIGP gene; congenital anomalies; glycosylphosphatidylinositol-anchored proteins; novel phenotype; whole-exome sequencing