Myotonic dystrophy type 1 cosegregating with autosomal dominant polycystic kidney disease type 2
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LETTER TO THE EDITOR
Myotonic dystrophy type 1 cosegregating with autosomal dominant polycystic kidney disease type 2 Tommaso Nicoletti 1,2 & Pietro Chiurazzi 3,4 & Marco Castori 5 & Alessia Perna 1,2 & Gabriella Silvestri 1,2 Received: 5 February 2020 / Accepted: 21 June 2020 # Fondazione Società Italiana di Neurologia 2020
Dear Editor, We report a genetic “double trouble” in a mother and daughter affected by both myotonic dystrophy type 1 (DM1) and autosomal dominant polycystic kidney disease (PKD). DM1, also known as Steinert disease (OMIM #160900), is the most common muscular dystrophy in adults with a prevalence of ~ 1:8000 among Caucasians. DM1 is caused by a large expansion of an unstable trinucleotide (CTG) within the 3′ UTR of DMPK gene (OMIM *605377). The DMPK transcript, containing the large expansion with hundreds of CUG triplets, has a toxic gain-of-function effect ultimately leading to the aberrant splicing of several target genes. DM1 is a progressive and multisystem disorder that, besides causing myotonia and progressive muscle atrophy, affects several other tissues and associates with type 2 diabetes. Recently, an increased risk of cancer in DM1 patients has been reported, mainly affecting the uterus, thyroid and skin (basal cell carcinoma, melanoma) [1]. Autosomal dominant polycystic kidney disease (PKD) is the most common inherited cystic kidney disease (~ 3– 4:10000) and is responsible for 5–10% of end-stage renal failure cases requiring dialysis or kidney transplantation (OMIM #173900 and #613095). Mutations in PKD1
Tommaso Nicoletti and Pietro Chiurazzi contributed equally to this work. * Gabriella Silvestri [email protected] 1
Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy
2
UOC Neurologia, Fondazione Policlinico Universitario “A. Gemelli” IRCSS, 00168 Roma, Italy
3
Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore, Rome, Italy
4
UOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy
5
Divisione di Genetica Medica, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy
(OMIM *601313) and PKD2 (OMIM *173910), encoding polycystin 1 and polycystin 2, account for ~ 85% and ~ 15% of PKD cases, respectively. Variants in PKD2 usually associate with a later onset of symptoms and a slower rate of progression to renal failure. Polycystin 1 and polycystin 2 associate on the primary cilium/centrosome complex which protrudes from the apical surface of mammalian cells, including those of the tubular epithelium in kidneys, regulating multiple intracellular signalling pathways in response to mechanical stimuli. Like DM1, also PKD is a multisystem disease characterized by formation and progressive enlargement of cysts in the kidneys, liver and pancreas as well as cerebral aneurysms and cardiac valve abnormalities. A higher incidence of cancer (kidney, colon and liver) has also been reported in PKD patients [2]. The family tree is reported in Fig. 1; individuals shaded in gr
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