Mutations in PCDH21 cause autosomal recessive cone-rod dystrophy.
BACKGROUND
Cone-rod dystrophy is a retinal dystrophy with early loss of cone photoreceptors and a parallel or subsequent loss of rod photoreceptors. It may be syndromic, but most forms are non-syndromic with autosomal dominant, autosomal recessive or X-linked recessive inheritance.


RESULTS
We identified a small consanguineous family with six patients with cone-rod dystrophy from the Faroe Islands. Homozygosity mapping revealed a single homozygous locus of 4.2 Mb on chromosome 10q23.1-q23.2, encompassing 11 genes. All patients were homozygous for a 1-bp duplication in PCDH21, c.524dupA, which results in a frameshift and a premature stop codon (p.Q175QfsX47).


CONCLUSIONS
To our knowledge, this is the first report of mutations in PCDH21 as a cause of human disease. PCDH21 is highly expressed in the retinal photoreceptor cells. It encodes protocadherin 21, which belongs to the cadherin superfamily of large cell surface proteins characterised by a variable number of extracellular cadherin domains. A PCDH21 knockout mouse model has previously shown loss of photoreceptor cells and abnormal cone and rod function, similar to the findings in the patients.
Ostergaard
E
E
Department of Clinical Genetics 4062, National University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen 2100, Denmark. elsebet.ostergaard@dadlnet.dk
Batbayli
M
M
Duno
M
M
Vilhelmsen
K
K
Rosenberg
T
T
D000293:Adolescent; D000328:Adult; D000818:Animals; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D002675:Child, Preschool; D003241:Consanguinity; D003718:Denmark; D055724:Electrophysiological Phenomena; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D058499:Retinal Dystrophies / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics*
C442481:CDHR1 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D009419:Nerve Tissue Proteins
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