Title: Novel FRMD7 mutations and genomic rearrangement expand the molecular pathogenesis of X-linked idiopathic infantile nystagmus
Authors: AlMoallem, Basamat ×
Bauwens, Miriam
Walraedt, Sophie
Delbeke, Patricia
De Zaeytijd, Julie
Kestelyn, Philippe
Meire, Francoise
Janssens, Sandra
Van Cauwenbergh, Caroline
Verdin, Hannah
Hooghe, Sally
Coppieters, Frauke
Kumar Thakur, Prasoon
De Leeneer, Kim
Devriendt, Koenraad
Leroy, Bart P
De Baere, Elfride #
Issue Date: Feb-2015
Publisher: Association for Research in Vision and Ophthalmology
Series Title: Investigative Ophthalmology & Visual Science vol:Ahead of print
Article number: IOVS-14-15938
Abstract: Purpose: Idiopathic infantile nystagmus (IIN) (OMIM 31700) with X-linked inheritance is one of the most common forms of infantile nystagmus. Up to date three X-linked loci have been identified, Xp11.4-p11.3 (CASK), Xp22 (GPR143), and Xq26-q27 (FRMD7) respectively. Here, we investigated the role of mutations and copy number variations (CNV) of FRMD7 and GPR143 in the molecular pathogenesis of IIN in forty-nine unrelated Belgian probands. Methods: We set up a comprehensive molecular genetic workflow based on Sanger sequencing, targeted next generation sequencing (NGS) and CNV analysis using multiplex ligation-dependent probe amplification (MLPA) for FRMD7 (NM_194277.2) and GPR143 (NM_000273.2). Results: In 11/49 probands, nine unique FRMD7 changes were found, five of which are novel: frameshift mutation c.2036del, missense mutations c.801C>A and c.875T>C, splice site mutation c.497+5G>A, and one genomic rearrangement (1.29 Mb deletion) in a syndromic case. Additionally, four known mutations were found: c.70G>A, c.886G>C, c.910C>T, and c.660del. The latter was found in three independent families. In silico predictions and segregation testing of the novel mutations support their pathogenic effect. No GPR143 mutations or CNVs were found in the remainder of the probands (38/49). Conclusions: Overall, genetic defects of FRMD7 were found in 11/49 (22.4%) probands, including the first reported genomic rearrangement of FRMD7 in IIN, expanding its mutational spectrum. Finally, we generate a discovery cohort of IIN patients potentially harboring either hidden variation of FRMD7 or mutations in genes at known or novel loci sustaining the genetic heterogeneity of IIN.
ISSN: 0146-0404
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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