The molecular basis of Kufs disease is unknown, whereas a series of genes accounting for most of the childhood onset forms of neuronal ceroid lipofuscinosis (NCL) have been identified. Diagnosis of Kufs disease is difficult because the characteristic lipopigment is largely confined to neurons and may require brain biopsy or autopsy for final diagnosis. We mapped 4 families with Kufs disease where there was good evidence for autosomal recessive inheritance, and found two peaks on chromosome 15. Three of the families had type A Kufs disease (presenting with progressive myoclonus epilepsy) and one had type B (presenting with dementia and motor system features). Sequencing of a candidate gene in one peak shared by all four families was unrewarding but sequencing of CLN6, found in the second peak and shared only by the three type A pedigrees revealed pathogenic mutations in all three. We subsequently sequenced CLN6 in eight other families, three with recessive type A Kufs disease. Mutations in both CLN6 alleles were found in the three type A cases and in one family with unclassified Kufs disease. Mutations in CLN6 are the major cause of recessive type A Kufs disease. The phenotypic differences between variant late infantile NCL, previously found to be caused by CLN6, and type A Kufs disease are striking with a much later age of onset and lack of visual involvement in the latter. Sequencing of CLN6 will provide a simple diagnostic strategy in this disorder where definitive identification usually requires invasive biopsy.

Kufs Disease, the Major Adult Form of Neuronal Ceroid Lipofuscinosis, Caused by Mutations in CLN6 / T., Arsov; K. R., Smith; J., Damiano; S., Franceschetti; L., Canafoglia; C. J., Bromhead; E., Andermann; D. F., Vears; P., Cossette; S., Rajagopalan; A., Mcdougall; V., Sofia; M., Farrell; U., Aguglia; A., Zini; Meletti, Stefano; M., Morbin; S., Mullen; F., Andermann; S. E., Mole; M., Bahlo; S. F., Berkovic. - In: AMERICAN JOURNAL OF HUMAN GENETICS. - ISSN 0002-9297. - STAMPA. - 88(5)(2011), pp. 566-573.

I documenti presenti in Iris Unimore sono rilasciati con licenza Creative Commons Attribuzione - Non commerciale - Non opere derivate 3.0 Italia, salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Powered by IRIS-about IRIS-Utilizzo dei cookie

 Copyright © 2021