Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina.
X-linked CSNB patients may exhibit myopia, nystagmus, strabismus and ERG abnormalities of the Schubert-Bornschein type. We recently identified the retina-specific L-type calcium channel alpha1 subunit gene CACNA1F localised to the Xp11.23 region, which is mutated in families showing the incomplete type (CSNB2). Here, we report comprehensive mutation analyses in the 48 CACNA1F exons in 36 families, most of them from Germany. All families were initially diagnosed as having the incomplete type of CSNB, except for two which have been designated as Aland Island eye disease (AIED)-like. Out of 33 families, a total of 30 different mutations were identified, of which 24 appear to be unique for the German population. The mutations, 20 of which are published here for the first time, were found to be equally distributed over the entire gene sequence. No mutation could be found in a classic AIED family previously shown to map to the CSNB2 interval. Cacna1f expression in photoreceptor-negative mice strains indicate that the gene is expressed in the outer nuclear, the inner nuclear, and the ganglion cell layer. Such a distribution points to the central role of calcium regulation in the interaction of retinal cells that mediate signal transmission.
Abteilung Medizinische Genetik der LMU, München, Germany.
Krisztina
K
Wutz
Christian
C
Sauer
Eberhart
E
Zrenner
Birgit
B
Lorenz
Tiina
T
Alitalo
Martina
M
Broghammer
Martin
M
Hergersberg
Albert
A
de la Chapelle
Bernhard H F
BH
Weber
Bernd
B
Wissinger
Alfons
A
Meindl
Carsten M
CM
Pusch
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015220:Calcium Channels / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000235:genetics; D020013:Calcium Signaling; D002874:Chromosome Mapping; D017931:DNA Primers; D005128:Eye Diseases / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009755:Night Blindness / Q000235:genetics; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D012160:Retina / Q000502:physiology*; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014960:X Chromosome
C113330:CACNA1F protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D017931:DNA Primers