Fine mapping of the X-linked recessive congenital idiopathic nystagmus locus at Xq24-q26.3.
OBJECTIVE
To refine the interval for X-linked congenital idiopathic nystagmus at Xq24-q26.3 and to evaluate a novel candidate gene (Muscleblind-like 3 gene [MBNL3]).


METHODS
A single pedigree with congenital idiopathic nystagmus (CIN) inherited as an X-linked recessive trait underwent detailed clinical examination including nystagmology and electrophysiological investigation in selected subjects. Following detailed phenotyping, genotyping was performed using 52 microsatellite markers spaced at an average of 5 cM along the X chromosome. Subsequent two-point and multipoint linkage analysis were performed and a candidate gene was screened for mutations by conventional sequencing.


RESULTS
Linkage mapping located the disease gene to a 15.5cM interval at Xq24-q26.3, between markers DXS1212 and DXS1062 with a maximum two-point LOD score of 4.24 with both markers DXS8044 and DXS994 (theta=0). Multipoint analysis indicated a LOD score of 4.54 and a critical gene interval of 8.0 cM. No mutations were found in the MBNL3 gene in this pedigree.


CONCLUSIONS
We describe a family with an unusual inheritance pattern most consistent with X-linked recessive inheritance with X inactivation causing manifesting females. We refine the linkage interval for X-linked recessive congenital idiopathic nystagmus and exclude MBNL3 as the causative gene in this family.
Self
James Edward
JE
Clinical Neurosciences Division, University of Southampton, Southampton, UK.
Ennis
Sarah
S
Collins
Andrew
A
Shawkat
Fatima
F
Harris
Christopher Mark
CM
Mackey
David Anthony
DA
Hodgkins
Peter Robert
PR
Temple
Isabelle Karen
IK
Chen
Xiaoli
X
Lotery
Andrew John
AJ
D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D050172:Genes, X-Linked; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D020417:Nystagmus, Congenital / Q000235:genetics*; D010375:Pedigree; D016601:RNA-Binding Proteins / Q000235:genetics*
C467324:MBNL3 protein, human; D016601:RNA-Binding Proteins