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Clinical and molecular characterization of de novo loss of function variants in HNRNPU
Author(s) -
Leduc Magalie S.,
Chao HsiaoTuan,
Qu Chunjing,
Walkiewicz Magdalena,
Xiao Rui,
Magoulas Pilar,
Pan Shujuan,
Beuten Joke,
He Weimin,
Bernstein Jonathan A.,
Schaaf Christian P.,
Scaglia Fernando,
Eng Christine M.,
Yang Yaping
Publication year - 2017
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38388
Subject(s) - microcephaly , intellectual disability , global developmental delay , agenesis of the corpus callosum , exome sequencing , loss function , corpus callosum , epilepsy , agenesis , genetics , phenotype , medicine , corpus callosum agenesis , biology , gene , pathology , psychiatry
DNA alterations in the 1q43‐q44 region are associated with syndromic neurodevelopmental disorders characterized by global developmental delay, intellectual disability, dysmorphic features, microcephaly, seizures, and agenesis of the corpus callosum. HNRNPU is located within the 1q43‐q44 region and mutations in the gene have been reported in patients with early infantile epileptic encephalopathy. Here, we report on the clinical presentation of four patients with de novo heterozygous HNRNPU loss‐of‐function mutations detected by clinical whole exome sequencing: c.651_660del (p.Gly218Alafs*118), c.1089G>A (p.Trp363*), c.1714C>T (p.Arg572*), and c.2270_2271del (p.Pro757Argfs*7). All patients shared similar clinical features as previously reported including seizures, global developmental delay, intellectual disability, variable neurologic regression, behavior issues, and dysmorphic facial features. Features including heart defects and kidney abnormalities were not reported in our patients. These findings expands the clinical spectrum of HNRNPU ‐related disorder and shows that HNRNPU contributes to a subset of the clinical phenotypes associated with the contiguous 1q43‐q44 deletion syndrome.