OBJECTIVE: Mutations of the genes encoding subunits of potassium voltage-gated channel, KCNQ2 and KCNQ3, have been identified in patients with benign familial neonatal seizures (BFNS). This study set out to determine the frequency of microchromosomal deletions of KCNQ2 or KCNQ3 associated with BFNS. METHODS: The study subjects were patients with BFNS (n = 22). Microdeletions were sought by multiplex ligation-dependent probe amplification and then confirmed by fluorescence in situ hybridization and characterized by array-based comparative genomic hybridization. RESULTS: Heterozygous multiple exonic deletions of KCNQ2 were identified in 4 of 22 patients with BFNS. Concomitant deletions of adjacent genes, including nicotinic cholinergic receptor alpha4 (CHRNA4), were detected in 2 of the 4 cases. The clinical courses of patients with deletions of both KCNQ2 and CHRNA4 were those of typical BFNS, and none presented with the phenotype of autosomal dominant nocturnal frontal lobe epilepsy, some of which are caused by mutations of CHRNA4. CONCLUSIONS: Our findings indicate that the clinical courses of patients with deletions of both KCNQ2 and CHRNA4 are indistinguishable from those of patients with deletions of KCNQ2 only.
OBJECTIVE: Mutations of the genes encoding subunits of potassium voltage-gated channel, KCNQ2 and KCNQ3, have been identified in patients with benign familial neonatal seizures (BFNS). This study set out to determine the frequency of microchromosomal deletions of KCNQ2 or KCNQ3 associated with BFNS. METHODS: The study subjects were patients with BFNS (n = 22). Microdeletions were sought by multiplex ligation-dependent probe amplification and then confirmed by fluorescence in situ hybridization and characterized by array-based comparative genomic hybridization. RESULTS: Heterozygous multiple exonic deletions of KCNQ2 were identified in 4 of 22 patients with BFNS. Concomitant deletions of adjacent genes, including nicotinic cholinergic receptor alpha4 (CHRNA4), were detected in 2 of the 4 cases. The clinical courses of patients with deletions of both KCNQ2 and CHRNA4 were those of typical BFNS, and none presented with the phenotype of autosomal dominant nocturnal frontal lobe epilepsy, some of which are caused by mutations of CHRNA4. CONCLUSIONS: Our findings indicate that the clinical courses of patients with deletions of both KCNQ2 and CHRNA4 are indistinguishable from those of patients with deletions of KCNQ2 only.
Authors: Heather Olson; Yiping Shen; Jennifer Avallone; Beth R Sheidley; Rebecca Pinsky; Ann M Bergin; Gerard T Berry; Frank H Duffy; Yaman Eksioglu; David J Harris; Fuki M Hisama; Eugenia Ho; Mira Irons; Christina M Jacobsen; Philip James; Sanjeev Kothare; Omar Khwaja; Jonathan Lipton; Tobias Loddenkemper; Jennifer Markowitz; Kiran Maski; J Thomas Megerian; Edward Neilan; Peter C Raffalli; Michael Robbins; Amy Roberts; Eugene Roe; Caitlin Rollins; Mustafa Sahin; Dean Sarco; Alison Schonwald; Sharon E Smith; Janet Soul; Joan M Stoler; Masanori Takeoka; Wen-Han Tan; Alcy R Torres; Peter Tsai; David K Urion; Laura Weissman; Robert Wolff; Bai-Lin Wu; David T Miller; Annapurna Poduri Journal: Ann Neurol Date: 2014-06-13 Impact factor: 10.422