TY - JOUR
T1 - Two novel FAM20C variants in a family with raine syndrome
AU - Hernández-Zavala, Araceli
AU - Cortés-Camacho, Fernando
AU - Palma-Lara, Icela
AU - Godínez-Aguilar, Ricardo
AU - Espinosa, Ana María
AU - Pérez-Durán, Javier
AU - Villanueva-Ocampo, Patricia
AU - Ugarte-Briones, Carlos
AU - Serrano-Bello, Carlos Alberto
AU - Sánchez-Santiago, Paula Jesús
AU - Bonilla-Delgado, José
AU - Yáñez-López, Marco Antonio
AU - Victoria-Acosta, Georgina
AU - López-Ornelas, Adolfo
AU - Alonso-Themann, Patricia García
AU - Moreno, José
AU - Palacios-Reyes, Carmen
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/2
Y1 - 2020/2
N2 - 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 FAM20C 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 FAM20C 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.
AB - 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 FAM20C 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 FAM20C 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.
KW - FAM20C
KW - Histopathology
KW - Lethal Raine syndrome
KW - New variants
UR - http://www.scopus.com/inward/record.url?scp=85079887677&partnerID=8YFLogxK
U2 - 10.3390/genes11020222
DO - 10.3390/genes11020222
M3 - Artículo
C2 - 32093234
AN - SCOPUS:85079887677
SN - 2073-4425
VL - 11
JO - Genes
JF - Genes
IS - 2
M1 - 222
ER -