Two Novel <i>FAM20C</i> Variants in a Family with Raine Syndrome

• Main Authors: Araceli Hernández-Zavala, Fernando Cortés-Camacho, Icela Palma-Lara, Ricardo Godínez-Aguilar, Ana María Espinosa, Javier Pérez-Durán, Patricia Villanueva-Ocampo, Carlos Ugarte-Briones, Carlos Alberto Serrano-Bello, Paula Jesús Sánchez-Santiago, José Bonilla-Delgado, Marco Antonio Yáñez-López, Georgina Victoria-Acosta, Adolfo López-Ornelas, Patricia García Alonso-Themann, José Moreno, Carmen Palacios-Reyes
• Format: Article
• Language: English
• Published: MDPI AG 2020-02-01
• Series: Genes
• Subjects: lethal raine syndrome; <i>fam20c</i>; new variants; histopathology
• Online Access: https://www.mdpi.com/2073-4425/11/2/222

Two siblings from a Mexican family who carried lethal Raine syndrome are presented. A newborn term male (case 1) and his 21 gestational week brother (case 2), with a similar osteosclerotic pattern: generalized osteosclerosis, which is more evident in facial bones and cranial base. Prenatal findings at 21 weeks and histopathological features for case 2 are described. A novel combination of biallelic <i>FAM20C</i> pathogenic variants were detected, a maternal cytosine duplication at position 456 and a paternal deletion of a cytosine in position 474 in exon 1, which change the reading frame with a premature termination at codon 207 and 185 respectively. These changes are in concordance with a negative detection of the protein in liver and kidney as shown in case 2. Necropsy showed absence of pancreatic Langerhans Islets, which are reported here for the first time. Corpus callosum absence is added to the few reported cases of brain defects in Raine syndrome. This report shows two new <i>FAM20C</i> variants not described previously, and negative protein detection in the liver and the kidney. We highlight that lethal Raine syndrome is well defined as early as 21 weeks, including mineralization defects and craniofacial features. Pancreas and brain defects found here in FAM20C deficiency extend the functional spectrum of this protein to previously unknown organs.