Mutations in PCDH21 cause autosomal recessive cone-rod dystrophy

• Published in: Journal of Medical Genetics
• Language: English
• Published: BMJ Publishing Group Ltd. 2011
• Subjects: Clinical genetics; Ophthalmology; Faroe Islands
• Online Access: http://hdl.handle.net/2262/49813; https://doi.org/10.1136/jmg.2009.069120

Abstract Background: Cone-rod dystrophy is a retinal dystrophy with early loss of cone receptors and a parallel or subsequent loss of rod receptors. It may be syndromic, but most forms are non-syndromic and inherited in an autosomal dominant, autosomal recessive or X-linked recessive way. 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. [e-mail] (Ostergaard, Elsebet) Rigshospitalet - DENMARK (Ostergaard, Elsebet) Rigshospitalet - DENMARK (Batbayli, Mustafa) National University Hospital Rigshospitalet - DENMARK (Duno, Morten) Faroese National Hospital - DENMARK (Vilhelmsen, Kaj) DENMARK Received: 2009-05-21 Revised: 2009-12-19 Accepted: 2010-01-14