Universität zu Köln

Bramswig, Nuria C., Luedecke, Hermann-Josef, Hamdan, Fadi F., Altmueller, Janine, Beleggia, Filippo ORCID: 0000-0003-0234-7094, Elcioglu, Nursel H., Freyer, Catharine, Gerkes, Erica H., Demirkol, Yasemin Kendir, Knupp, Kelly G., Kuechler, Alma, Li, Yun, Lowenstein, Daniel H., Michaud, Jacques L., Park, Kristen, Stegmann, Alexander P. A., Veenstra-Knol, Hermine E., Wieland, Thomas, Wollnik, Bernd, Engels, Hartmut, Strom, Tim M., Kleefstra, Tjitske and Wieczorek, Dagmar (2017). Heterozygous HNRNPU variants cause early onset epilepsy and severe intellectual disability. Hum. Genet., 136 (7). S. 821 - 835. NEW YORK: SPRINGER. ISSN 1432-1203

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Abstract

Pathogenic variants in genes encoding subunits of the spliceosome are the cause of several human diseases, such as neurodegenerative diseases. The RNA splicing process is facilitated by the spliceosome, a large RNA-protein complex consisting of small nuclear ribonucleoproteins (snRNPs), and many other proteins, such as heterogeneous nuclear ribonucleoproteins (hnRNPs). The HNRNPU gene (OMIM *602869) encodes the heterogeneous nuclear ribonucleoprotein U, which plays a crucial role in mammalian development. HNRNPU is expressed in the fetal brain and adult heart, kidney, liver, brain, and cerebellum. Microdeletions in the 1q44 region encompassing HNRNPU have been described in patients with intellectual disability (ID) and other clinical features, such as seizures, corpus callosum abnormalities (CCA), and microcephaly. Recently, pathogenic HNRNPU variants were identified in large ID and epileptic encephalopathy cohorts. In this study, we provide detailed clinical information of five novels and review two of the previously published individuals with (likely) pathogenic de novo variants in the HNRNPU gene including three non-sense and two missense variants, one small intragenic deletion, and one duplication. The phenotype in individuals with variants in HNRNPU is characterized by early onset seizures (6/7), severe ID (6/6), severe speech impairment (6/6), hypotonia (6/7), and central nervous system (CNS) (5/6), cardiac (4/6), and renal abnormalities (3/4). In this study, we broaden the clinical and mutational HNRNPU-associated spectrum, and demonstrate that heterozygous HNRNPU variants cause epilepsy, severe ID with striking speech impairment and variable CNS, cardiac, and renal anomalies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bramswig, Nuria C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Luedecke, Hermann-Josef UNSPECIFIED UNSPECIFIED UNSPECIFIED Hamdan, Fadi F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Beleggia, Filippo UNSPECIFIED orcid.org/0000-0003-0234-7094 UNSPECIFIED Elcioglu, Nursel H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Freyer, Catharine UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerkes, Erica H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Demirkol, Yasemin Kendir UNSPECIFIED UNSPECIFIED UNSPECIFIED Knupp, Kelly G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuechler, Alma UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Yun UNSPECIFIED UNSPECIFIED UNSPECIFIED Lowenstein, Daniel H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Michaud, Jacques L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Park, Kristen UNSPECIFIED UNSPECIFIED UNSPECIFIED Stegmann, Alexander P. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Veenstra-Knol, Hermine E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wieland, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Wollnik, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Engels, Hartmut UNSPECIFIED UNSPECIFIED UNSPECIFIED Strom, Tim M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleefstra, Tjitske UNSPECIFIED UNSPECIFIED UNSPECIFIED Wieczorek, Dagmar UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-226635
DOI:	10.1007/s00439-017-1795-6
Journal or Publication Title:	Hum. Genet.
Volume:	136
Number:	7
Page Range:	S. 821 - 835
Date:	2017
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COPY-NUMBER VARIATION; DE-NOVO MUTATIONS; CORPUS-CALLOSUM; CANDIDATE GENES; CRITICAL REGION; DELETION; 1Q44; SEIZURES; ENCEPHALOPATHIES; ABNORMALITIES Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22663