titoli, abstracts, parole chiave >>>
Novel SPAST deletion and reduced DPY30 expression in a spastic paraplegia type 4 kindred

Racis, Loretta and Storti, Eugenia and Pugliatti, Maura and Agnetti, Virgilio and Tessa, Alessandra and Santorelli, Filippo M. (2014) Novel SPAST deletion and reduced DPY30 expression in a spastic paraplegia type 4 kindred. BMC Medical Genetics, Vol. 15 , [Article] 39. eISSN 1471-2350. Article.

[img]
Preview
Full text disponibile come PDF Richiede visualizzatore di PDF come GSview, Xpdf o Adobe Acrobat Reader
Available under License Creative Commons Attribution.

681Kb

DOI: 10.1186/1471-2350-15-39

Abstract

Background: The hereditary spastic paraplegias (HSPs) are pleiomorphic disorders of motor pathway and a large number of affected genes have been discovered. Yet, mutations in SPG4/SPAST represent the most frequent molecular etiology in autosomal dominant (AD) patients and sporadic cases. We describe a large, AD-HSP Sardinian family where 5 out of several living members harbored a novel deletion affecting also the 5′UTR of SPAST and resulting in reduced expression of DPY30, the gene located upstream SPAST in a head-to-head manner.
Case presentation: A 54-year-old woman manifested leg stiffness at age 39 and required a cane to walk at age 50. Neurological examination disclosed mild spasticity and weakness in the legs, hyperreflexia in all limbs, and bilateral Babinski sign. She also complained of urinary urgency, but no additional neurological symptoms or signs were detected at examination. The clinical examination of 24 additional relatives disclosed three further affected individuals, two men and one woman. In the four symptomatic patients the initial manifestations were walking abnormalities and leg stiffness with a mean age at onset (SD) of 46.75 (5.44) years (range 39–51). The mean disease duration was 13.2 (13.4) years (range 6–35), and it correlated well with clinical severity (SPRS score) (r = 0.975, p = 0.005). One patient was confined to bed and displayed knee and ankle contractures, another case needed a cane to walk, and two individuals were able to walk without aids. Interestingly, a patient had also had a miscarriage during her first pregnancy.
Gene testing revealed an heterozygous deletion spanning from the 5′-UTR to intron 4 of SPAST in the affected individuals and in one clinically unaffected woman. In three affected patients, the deletion also determined low mRNA levels of SPAST and DPY30, a component of the Set1-like multiprotein histone methyltransferase complex located upstream, head-to-head with SPAST.
Conclusion: Together with data described in a Japanese family, our findings seem to suggest that genes close to spastin might be candidates in modulating the clinical phenotype. This report endorses future research on the role of neighboring genes as potential players in SPG4 disease variability.

Item Type:Article
ID Code:9751
Status:Published
Refereed:Yes
Uncontrolled Keywords:SPG4, DPY30, genetic modifier, deletion
Subjects:Area 06 - Scienze mediche > MED/26 Neurologia
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Medicina Clinica e Sperimentale
Publisher:BioMed Central
eISSN:1471-2350
Copyright Holders:© 2014 Racis et al.; licensee BioMed Central Ltd.
Deposited On:10 Apr 2014 13:14

I documenti depositati in UnissResearch sono protetti dalle leggi che regolano il diritto d'autore

Repository Staff Only: item control page