Mutations in PCDH21 cause autosomal recessive cone-rod dystrophy

• Published in: Journal of Medical Genetics
• Main Authors: Ostergaard, E, Batbayli, M, Duno, M, Vilhelmsen, K, Rosenberg, T
• Format: Text
• Language: English
• Published: British Medical Journal Publishing Group 2010
• Subjects: Original article; Faroe Islands
• Online Access: http://jmg.bmj.com/cgi/content/short/47/10/665; https://doi.org/10.1136/jmg.2009.069120

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. Methods and 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). Conclusion 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.