TY - JOUR
T1 - Three de novo DDX3X variants associated with distinctive brain developmental abnormalities and brain tumor in intellectually disabled females
AU - TUDP consortium
AU - Scala, Marcello
AU - Torella, Annalaura
AU - Severino, Mariasavina
AU - Morana, Giovanni
AU - Castello, Raffaele
AU - Accogli, Andrea
AU - Verrico, Antonio
AU - Vari, Maria Stella
AU - Cappuccio, Gerarda
AU - Pinelli, Michele
AU - Vitiello, Giuseppina
AU - Terrone, Gaetano
AU - D'Amico, Alessandra
AU - Nigro, Vincenzo
AU - Capra, Valeria
PY - 2019/8
Y1 - 2019/8
N2 - De novo DDX3X variants account for 1-3% of syndromic intellectual disability (ID) in females and have been occasionally reported in males. Furthermore, somatic DDX3X variants occur in several aggressive cancers, including medulloblastoma. We report three unrelated females with severe ID, dysmorphic features, and a common brain malformative pattern characterized by malformations of cortical development, callosal dysgenesis, basal ganglia anomalies, and midbrain-hindbrain malformations. A pilocytic astrocytoma was incidentally diagnosed in Patient 1 and trigonocephaly was found in Patient 2. With the use of family based whole exome sequencing (WES), we identified three distinct de novo variants in DDX3X. These findings expand the phenotypic spectrum of DDX3X-related disorders, demonstrating unique neuroradiological features resembling those of the tubulinopathies, and support a role for DDX3X in neuronal development. Our observations further suggest a possible link between germline DDX3X variants and cancer development.
AB - De novo DDX3X variants account for 1-3% of syndromic intellectual disability (ID) in females and have been occasionally reported in males. Furthermore, somatic DDX3X variants occur in several aggressive cancers, including medulloblastoma. We report three unrelated females with severe ID, dysmorphic features, and a common brain malformative pattern characterized by malformations of cortical development, callosal dysgenesis, basal ganglia anomalies, and midbrain-hindbrain malformations. A pilocytic astrocytoma was incidentally diagnosed in Patient 1 and trigonocephaly was found in Patient 2. With the use of family based whole exome sequencing (WES), we identified three distinct de novo variants in DDX3X. These findings expand the phenotypic spectrum of DDX3X-related disorders, demonstrating unique neuroradiological features resembling those of the tubulinopathies, and support a role for DDX3X in neuronal development. Our observations further suggest a possible link between germline DDX3X variants and cancer development.
U2 - 10.1038/s41431-019-0392-7
DO - 10.1038/s41431-019-0392-7
M3 - Article
C2 - 30936465
VL - 27
SP - 1254
EP - 1259
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 8
ER -