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

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)×1) 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.

Prenatal Genome-Wide Cell-Free DNA Screening: Three Years of Clinical Experience in a Hospital Prenatal Diagnostic Unit in Spain.

Genome-wide prenatal cell-free DNA (cfDNA) screening can be used to screen for a wide range of fetal chromosomal anomalies in pregnant patients. In this study, we describe our clinical experience with a genome-wide cfDNA assay in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RAAs), and copy-number variations (CNVs) in about 6000 patients over a three-year period at our hospital's Prenatal Diagnostic Unit in Spain. Overall, 204 (3.3%) patients had a high-risk call, which included 76 trisomy 21, 21 trisomy 18, 7 trisomy 13, 29 SCAs, 31 RAAs, 31 CNVs, and 9 cases with multiple anomalies. The diagnostic outcomes were obtained for the high-risk cases when available, allowing for the calculation of positive predictive values (PPVs). Calculated PPVs were 95.9% for trisomy 21, 77.8% for trisomy 18, 66.7% for trisomy 13, 10.7% for RAAs, and 10.7% for CNVs. Pregnancy and birth outcomes were also collected for the majority of RAA and CNV cases. Adverse perinatal outcomes for some of these cases included preeclampsia, fetal growth restriction, preterm birth, reduced birth weight, and major congenital structural abnormalities. In conclusion, our study showed strong performance for genome-wide cfDNA screening in a large cohort of pregnancy patients in Spain.

Conocimiento de las técnicas de diagnóstico prenatal por parte de los médicos de atención primaria / Awareness of prenatal diagnosis methods among primary care physicians

En el año 2000, la Consejería de Salud de la Junta de Andalucía pone en marcha los procesos asistenciales integrados (PAI). El PAI correspondiente al embarazo, el parto y el puerperio, que implica tanto al médico de atención primaria como al obstetra, fue uno de los primeros en implantarse. Los avances en genética han propiciado una mejora en el diagnóstico precoz de anomalías genéticas, por ello es importante el conocimiento y la formación del médico de atención primaria en las técnicas de cribado. Objetivo: Valorar los conocimientos teóricos de los médicos de atención primaria sobre las técnicas de diagnóstico prenatal y si se consideran capacitados para ofrecer asesoramiento genético. Diseño: Estudio descriptivo transversal. Ámbito: Distritos sanitarios Valle del Guadalhorce (Málaga) y Condado-Campiña (Huelva). Población: Médicos de atención primaria de la zona que aceptaron participar, con exclusión de pediatras, médicos de urgencias y dispositivos de apoyo. Intervenciones: Mediante un cuestionario se evaluaron los conocimientos de los médicos de atención primaria y su percepción consciente en cuanto a su falta de conocimiento en el tema. Participaron 108 médicos, y se obtuvieron 100 cuestionarios válidos. Los datos se analizaron con el paquete estadístico SPSS 13.0 Windows. Conclusiones: Existe un alto índice de desconocimiento sobre las técnicas de diagnóstico prenatal por parte de los médico de atención primaria...