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Titre	Novel and known FRMD7 mutations and genomic rearrangement in Belgian patients with X-linked idiopathic infantile nystagmus
Abstract Nr.	1019

But	FRMD7-related infantile nystagmus (FIN) represent 50% of cases with X-linked IN. Thus far 45 unique FRMD7 mutations have been reported in FIN, all of which are coding mutations apart from one partial gene deletion. Here, we investigated the role of FRMD7 mutations and copy number variations (CNV) in the molecular pathogenesis of IIN in forty-nine unrelated Belgian probands.
Méthodes	We set up a comprehensive molecular genetic workflow based on Sanger sequencing, targeted next generation sequencing (NGS) and CNV analysis of FRMD7 (NM_194277.2).
Résultats	In elven unrelated probands, nine unique FRMD7 changes were found, five of which are novel: frameshift mutation c.2036del p.(Leu679Argfs8), missense mutations c.801C>A p.(Phe267Leu) and c.875T>C p.( Leu292Pro), splice site mutation c.497+5G>A, and one genomic rearrangement, being a 1.29 Mb deletion found in a syndromic case. Additionally, four known mutations were found: c.70G>A p.(Gly24Arg), c.886G>C p.(Gly296Arg), c.910C>T p.(Arg303), and c.660del p.(Asn221Ilefs*11). The latter was found in three independent families. Haplotype reconstruction suggests a potential founder effect. In silico predictions and segregation testing of these mutations support their pathogenic effect.
Conclusion	Overall, we found both coding FRMD7 mutations and a CNV in 11/49 Belgian families with IIN (22.5%) and expand the mutational spectrum of FRMD7 in IIN. Finally, our study generates a discovery cohort of IIN patients harboring either undetected mutations in non-coding region of FRMD7 or in genes at known or novel loci sustaining the genetic heterogeneity of the disease.

Auteur 1

Nom	ALMOALLEM
Initiales	B
Institut	Ctr.for Med.Genetics,Ghent University Hospital
Ville	Ghent

Auteur 2

Nom	Walraedt
Initiales	S
Institut	Dept. of Ophtha.
Ville	Ghent

Auteur 3

Nom	Delbeke
Initiales	P
Institut	Dept. of Ophtha.
Ville	Ghent

Auteur 4

Nom	Leroy
Initiales	BP
Institut	Dept. of Ophtha.
Ville	Ghent

Auteur 5

Nom	De Baere
Initiales	E
Institut	Ctr.for Med.Genetics
Ville	Ghent