Screening for spinocerebellar ataxia type 36 (SCA36) in greek patients

Postgraduate Thesis uoadl:2896242 24 Read counter

Unit:
Κατεύθυνση Βασική Έρευνα
Library of the School of Health Sciences
Deposit date:
2020-02-14
Year:
2020
Author:
Katsimpouris Dimitrios
Supervisors info:
Καραδήμα Γεωργία, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, Ε.Κ.Π.Α., Επιβλέπουσα
Κούτσης Γεώργιος, Επίκουρος Καθηγητής, Ιατρική Σχολή, Ε.Κ.Π.Α.
Κουτσιλιέρης Μιχαήλ, Καθηγητής, Ιατρική Σχολή, Ε.Κ.Π.Α.
Original Title:
Μελέτη της νωτιαιοπαρεγκεφαλιδικής αταξίας τύπου 36 (SCA36) σε Έλληνες ασθενείς
Languages:
Greek
Translated title:
Screening for spinocerebellar ataxia type 36 (SCA36) in greek patients
Summary:
Spinocerebellar ataxia type 36 (SCA36) is an autosomal dominant (AD) disorder, clinically characterized by late onset cerebellar ataxia usually between 5th and 6th decade of life, dysarthria, sensorineural hearing loss (SNHL), lower motor neuron involvement, and tongue atrophy.
A hexanucleotide repeat expansion, namely GGCCTG in intron 1 of the NOP56 gene, was reported in 2011 as the cause of the disease. Normal size alleles vary from 3 to 14 repeats, alleles of uncertain significance from 15 to 650 repeats and pathogenic alleles have more than 650 repeats.
The highest frequencies worldwide have been reported in clusters of affected families in specific geographical areas (Galicia-Spain, Italy, Han Chinese, East and West Japan).
The aim of current study was to investigate the presence of hexanucleotide repeat GGCCTG causing SCA36 in a cohort of Greek ataxia patients.
Our cohort consisted of 98 selected index patients. 92 patients came from an ataxia cohort (n=600), negative for the most common SCAs (SCA1, SCA2, SCA3, SCA6, SCA7), with pedigree and phenotype consistent with SCA36 and 6 came from a suspected Kennedy’s disease cohort (n=200), negative for the CAG trinucleotide repeat in AR and pedigree consistent with SCA36. The number of GGCCTG hexanucleotide repeats was determined with conventional PCR for the smaller alleles and RP-PCR for the larger alleles. Fragment length analysis was performed and positive controls were used in every run.
Supplementary to our previous study of AD spinocerebellar ataxias in the Greek population, we screened a less common gene causing inherited ataxia. In line with SCA3, SCA36 seems to be a very rare finding in the Greek population. SCA36 frequency in Greece appears to be similar to Germany, Portugal and UK reinforcing the findings of an uneven distribution in Europe. The absence of SCA36 in Greece supports the theory of disease clusters and amplifies the possibility of founder effect. The normal range of repeats detected was slightly narrower than reported in literature.
The present study could contribute to the investigation of the genetic heterogeneity of SCAs in the Greek population. Testing for SCA36 should only be performed following the exclusion of other more common SCAs in Greek patient cohorts.
Main subject category:
Health Sciences
Keywords:
Spinocerebellar ataxia type 36, SCA36, Hexanucleotide repeat disorder, Autosomal dominant cerebellar ataxia, Greek population
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
53
Number of pages:
87
ΔΙΠΛΩΜΑΤΙΚΗ ΕΡΓΑΣΙΑ ΚΑΤΣΙΜΠΟΥΡΗ ΔΗΜΗΤΡΙΟΥ.pdf (3 MB) Open in new window