Mutations in PCDH21 cause autosomal recessive cone-rod dystrophy

International audience 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 w...

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Bibliographic Details
Published in:Journal of Medical Genetics
Main Authors: Ostergaard, Elsebet, Batbayli, Mustafa, Duno, Morten, Vilhelmsen, Kaj
Other Authors: Rigshospitalet Copenhagen, Copenhagen University Hospital, National University Hospital Rigshospitalet, Faroese National Hospital
Format: Article in Journal/Newspaper
Language:English
Published: HAL CCSD 2010
Subjects:
Clinical genetics
Ophthalmology
Faroe Islands
Online Access:https://hal.archives-ouvertes.fr/hal-00560776
https://hal.archives-ouvertes.fr/hal-00560776/document
https://hal.archives-ouvertes.fr/hal-00560776/file/PEER_stage2_10.1136%252Fjmg.2009.069120.pdf
https://doi.org/10.1136/jmg.2009.069120
Description
Summary:International audience 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.

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