,Identification and functional characterization of a novel missense mutation in FRMD7 responsible fo

• 作 者: Zhe Wang Min Wang Chengyan Wang Boyang Lu
• 机 构: Department of Ophthalmology, Central Hospital of Zibo, Zibo 255036, China“,”Department of Pathology,
• 出 处: 生物化学与生物物理学报（英文版）
• 发表日期: 2019年2期
• 关键词: idiopathic congenital nystagmus FRMD7 missense c.805A ＞ C CASK

Idiopathic congenital nystagmus (ICN) is a genetically heterogeneous eye movement disorder which seriously reduces childhood visual acuity.X-linked inheritance is the most common patte,and mutations in FERM domain-containing protein 7 (FRMD7) are the major cause.Here,we recruited a four-generation Chinese family with X-linked ICN for the causative mutational screening of FRMD7.A novel missense variant,c.805 A ＞ C,was identified in the proband.The mutation was confirmed in all the affected individuals but was not detected in unaffected family members or 100 unrelated Chinese male controls.The mutation causes a substitution of lysine to glutamine at position 269 (p.Lys269GIn,K269Q).The FRMD7 mutant inhibits the formation and extension of neurites.Moreover,the mutation disrupts FRMD7 interaction with calcium/calmodulin-dependent serine protein kinase and neurite formation.Together,our data expand the mutation spectrum of FRMD7 causing ICN and provide an insight into the pathogenesis of nystagmus.