TY - JOUR
T1 - Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: expanding the spectrum of PRPS1-related disorders
AU - Al-Maawali, Almundher
AU - Dupuis, Lucie
AU - Blaser, Susan
AU - Heon, Elise
AU - Tarnopolsky, Mark
AU - Al-Murshedi, Fathiya
AU - Marshall, Christian R.
AU - Paton, Tara
AU - Scherer, Stephen W.
AU - Roelofsen, Jeroen
AU - van Kuilenburg, André B. P.
AU - Mendoza-Londono, Roberto
AU - AUTHOR GROUP
AU - Boycott, Kym
AU - Friedman, Jan
AU - Michaud, Jacques
AU - Bernier, Francois
AU - Brudno, Michael
AU - Fernandez, Bridget
AU - Knoppers, Bartha
AU - Samuels, Mark
AU - Scherer, Steve
AU - Marcadier, Janet
AU - Beaulieu, Chandree
PY - 2015
Y1 - 2015
N2 - PRPS1 codes for the enzyme phosphoribosyl pyrophosphate synthetase-1 (PRS-1). The spectrum of PRPS1-related disorders associated with reduced activity includes Arts syndrome, Charcot-Marie-Tooth disease-5 (CMTX5) and X-linked non-syndromic sensorineural deafness (DFN2). We describe a novel phenotype associated with decreased PRS-1 function in two affected male siblings. Using whole exome and Sanger sequencing techniques, we identified a novel missense mutation in PRPS1. The clinical phenotype in our patients is characterized by high prenatal maternal α-fetoprotein, intrauterine growth restriction, dysmorphic facial features, severe intellectual disability and spastic quadraparesis. Additional phenotypic features include macular coloboma-like lesions with retinal dystrophy, severe short stature and diabetes insipidus. Exome sequencing of the two affected male siblings identified a shared putative pathogenic mutation c.586C>T p.(Arg196Trp) in the PRPS1 gene that was maternally inherited. Follow-up testing showed normal levels of hypoxanthine in urine samples and uric acid levels in blood serum. The PRS activity was significantly reduced in erythrocytes of the two patients. Nucleotide analysis in erythrocytes revealed abnormally low guanosine triphosphate and guanosine diphosphate. This presentation is the most severe form of PRPS1-deficiency syndrome described to date and expands the spectrum of PRPS1-related disorders
AB - PRPS1 codes for the enzyme phosphoribosyl pyrophosphate synthetase-1 (PRS-1). The spectrum of PRPS1-related disorders associated with reduced activity includes Arts syndrome, Charcot-Marie-Tooth disease-5 (CMTX5) and X-linked non-syndromic sensorineural deafness (DFN2). We describe a novel phenotype associated with decreased PRS-1 function in two affected male siblings. Using whole exome and Sanger sequencing techniques, we identified a novel missense mutation in PRPS1. The clinical phenotype in our patients is characterized by high prenatal maternal α-fetoprotein, intrauterine growth restriction, dysmorphic facial features, severe intellectual disability and spastic quadraparesis. Additional phenotypic features include macular coloboma-like lesions with retinal dystrophy, severe short stature and diabetes insipidus. Exome sequencing of the two affected male siblings identified a shared putative pathogenic mutation c.586C>T p.(Arg196Trp) in the PRPS1 gene that was maternally inherited. Follow-up testing showed normal levels of hypoxanthine in urine samples and uric acid levels in blood serum. The PRS activity was significantly reduced in erythrocytes of the two patients. Nucleotide analysis in erythrocytes revealed abnormally low guanosine triphosphate and guanosine diphosphate. This presentation is the most severe form of PRPS1-deficiency syndrome described to date and expands the spectrum of PRPS1-related disorders
U2 - https://doi.org/10.1038/ejhg.2014.112
DO - https://doi.org/10.1038/ejhg.2014.112
M3 - Article
C2 - 24961627
SN - 1018-4813
VL - 23
SP - 310
EP - 316
JO - European journal of human genetics
JF - European journal of human genetics
IS - 3
ER -