Affiliations: Institute of Human Genetics, RWTH Aachen, Aachen,
Germany | Institute of Neuropathology, RWTH Aachen, Aachen,
Germany | Institute of Human Genetics, University of Bonn, Bonn,
Germany | Friedrich-Baur-Institute, Ludwig-Maximilians
University Munich, Munich, Germany
Note: [] Correspondence: Andreas Roos, PhD, Institute of Neuropathology,
Medical Faculty, RWTH Aachen University, Pauwelsstr. 30 D-52074 Aachen,
Germany. Tel.: +49 241 8037084; Fax: +49 241 8082394; E-mail:
[email protected]
Abstract: Marinesco-Sjögren syndrome (MSS) is a multiorgan disorder
firstly described in 1931 by Gheorge Marinescu. During the last seven decades,
research into the clinical picture of MSS has led to the description of varying
MSS phenotypes and since 2005, it is known that mutations within the SIL1 gene
cause MSS in a part of these patients. Among these "SIL1-related MSS cases",
"classical and non-classical phenotypes" are distinguished. All "SIL1-related
MSS cases" show at least an ataxia due to cerebellar atrophy, congenital or
infantile cataracts and a progressive myopathy as well as mental impairment
("classical MSS phenotype"). Additional clinical features are for example in
some cases short stature, hypogonadism, scoliosis, nystagmus and strabismus
("non-classical MSS phenotype"). However, the primary pathology has remained
unknown in non-SIL1-related MSS cases. As the clinical features detected in
"classical MSS phenotype" and "non-classical MSS phenotype" may also be
associated with cryptic subtelomeric rearrangements and as a frequent
localization of for example cataract-related genes/loci within these regions is
proven, we performed subtelomere screening in a series of 23 patients with
"non-SIL1-related non-classical MSS phenotypes" presenting with at least three
features like early cataracts, mental retardation, brain malformations,
muscular hypotonia, growth retardation and skeletal abnormalities. Karyotype
and the SIL1 coding sequence were normal in all cases. Subtelomere screening by
multiplex ligation-dependent probe amplification did not identify any
subtelomeric imbalances. Therefore, a causative role of these regions in
manifesting "non-SIL1-related non-classical MSS phenotypes" seems to be
unlikely.
