PURPOSE: To identify mutations causing X-linked congenital motor nystagmus (XL-CMN) in Chinese families. METHODS: Genomic DNA was prepared from peripheral blood leukocytes. Cycle sequencing was used to detect the sequence variation of the FERM domain containing 7 (FRMD7) gene, where mutations have been identified recently to associate with XL-CMN. RESULTS: Sequencing of the coding and the adjacent intron regions of FRMD7 identified mutations in four families with XL-CMN, c.41-43delAGA (p.Lys14del) in exon 1, c.70G>A (p.Gly24Arg) in exon 2, c.436C>T (p.Arg146Trp) in exon 6, and c.685C>T (p.Arg229Cys) in exon 8, respectively, where the last two were novel. These mutations were not detected in 196 normal controls. In the two families with X-linked recessive CMN, females carrying a heterozygous mutation in FRMD7 did not have any sign of nystagmus. CONCLUSIONS: Our results provide additional evidence for mutations in FRMD7 as a common cause of XL-CMN and expand its mutation spectrum. CMN in a Chinese family with pure X-linked recessive pattern, previously mapped to Xq23-q27, is associated with the c.41-43delAGA mutation in FRMD7.
PURPOSE: To identify mutations causing X-linked congenital motor nystagmus (XL-CMN) in Chinese families. METHODS: Genomic DNA was prepared from peripheral blood leukocytes. Cycle sequencing was used to detect the sequence variation of the FERM domain containing 7 (FRMD7) gene, where mutations have been identified recently to associate with XL-CMN. RESULTS: Sequencing of the coding and the adjacent intron regions of FRMD7 identified mutations in four families with XL-CMN, c.41-43delAGA (p.Lys14del) in exon 1, c.70G>A (p.Gly24Arg) in exon 2, c.436C>T (p.Arg146Trp) in exon 6, and c.685C>T (p.Arg229Cys) in exon 8, respectively, where the last two were novel. These mutations were not detected in 196 normal controls. In the two families with X-linked recessive CMN, females carrying a heterozygous mutation in FRMD7 did not have any sign of nystagmus. CONCLUSIONS: Our results provide additional evidence for mutations in FRMD7 as a common cause of XL-CMN and expand its mutation spectrum. CMN in a Chinese family with pure X-linked recessive pattern, previously mapped to Xq23-q27, is associated with the c.41-43delAGA mutation in FRMD7.
Authors: Mervyn G Thomas; Moira Crosier; Susan Lindsay; Anil Kumar; Shery Thomas; Masasuke Araki; Chris J Talbot; Rebecca J McLean; Mylvaganam Surendran; Katie Taylor; Bart P Leroy; Anthony T Moore; David G Hunter; Richard W Hertle; Patrick Tarpey; Andrea Langmann; Susanne Lindner; Martina Brandner; Irene Gottlob Journal: Brain Date: 2011-02-08 Impact factor: 13.501