TY  - JOUR
A1  - Farag, Heba Gamal
A1  - Froehler, Sebastian
A1  - Oexle, Konrad
A1  - Ravindran, Ethiraj
A1  - Schindler, Detlev
A1  - Staab, Timo
A1  - Huebner, Angela
A1  - Kraemer, Nadine
A1  - Chen, Wei
A1  - Kaindl, Angela M.
T1  - Abnormal centrosome and spindle morphology in a patient with autosomal recessive primary microcephaly type 2 due to compound heterozygous WDR62 gene mutation
JF  - Orphanet Journal of Rare Diseases
N2  - Background: Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disease with severe microcephaly at birth due to a pronounced reduction in brain volume and intellectual disability. Biallelic mutations in the WD repeat-containing protein 62 gene WDR62 are the genetic cause of MCPH2. However, the exact underlying pathomechanism of MCPH2 remains to be clarified. 
Methods/results: We characterized the clinical, radiological, and cellular features that add to the human MCPH2 phenotype. Exome sequencing followed by Sanger sequencing in a German family with two affected daughters with primary microcephaly revealed in the index patient the compound heterozygous mutations c. 1313G>A (p.R438H) / c.2864-2867delACAG (p.D955Afs*112) of WDR62, the second of which is novel. Radiological examination displayed small frontal lobes, corpus callosum hypoplasia, simplified hippocampal gyration, and cerebellar hypoplasia. We investigated the cellular phenotype in patient-derived lymphoblastoid cells and compared it with that of healthy female controls. WDR62 expression in the patient's immortalized lymphocytes was deranged, and mitotic spindle defects as well as abnormal centrosomal protein localization were apparent. 
Conclusion: We propose that a disruption of centrosome integrity and/or spindle organization may play an important role in the development of microcephaly in MCPH2.
KW  - cell division
KW  - intellectual disability
KW  - missense mutations
KW  - protein
KW  - malformations
KW  - establishment
KW  - cytokinesis
KW  - genome
KW  - midbody
KW  - database
KW  - maintenance
KW  - families
KW  - microcephaly
KW  - WDR62 mutation
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123505
SN  - 1750-1172
VL  - 8
IS  - 178
ER  - 
TY  - JOUR
A1  - von Bernuth, Horst
A1  - Ravindran, Ethiraj
A1  - Du, Hang
A1  - Froehler, Sebastian
A1  - Strehl, Karoline
A1  - Kraemer, Nadine
A1  - Issa-Jahns, Lina
A1  - Amulic, Borko
A1  - Ninnemann, Olaf
A1  - Xiao, Mei-Sheng
A1  - Eirich, Katharina
A1  - Koelsch, Uwe
A1  - Hauptmann, Kathrin
A1  - John, Rainer
A1  - Schindler, Detlev
A1  - Wahn, Volker
A1  - Chen, Wei
A1  - Kaindl, Angela M.
T1  - Combined immunodeficiency develops with age in Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (ICF2)
JF  - Orphanet Journal of Rare Dieeases
N2  - The autosomal recessive immunodeficiency-centromeric instability-facial anomalies syndrome (ICF) is characterized by immunodeficiency, developmental delay, and facial anomalies. ICF2, caused by biallelic ZBTB24 gene mutations, is acknowledged primarily as an isolated B-cell defect. Here, we extend the phenotype spectrum by describing, in particular, for the first time the development of a combined immune defect throughout the disease course as well as putative autoimmune phenomena such as granulomatous hepatitis and nephritis. We also demonstrate impaired cell-proliferation and increased cell death of immune and non-immune cells as well as data suggesting a chromosome separation defect in addition to the known chromosome condensation defect.
KW  - ZBTB24
KW  - ICF2
KW  - granulomas
KW  - facial anomalies
KW  - centromeric instability
KW  - intellectual disability
KW  - lymphoma
KW  - ZBTB24 mutations
KW  - DNMT3B
KW  - TYPE-2
KW  - immunodeficiency
KW  - microcephaly
KW  - DNA methyltransferase gene
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114859
VL  - 9
ER  -