A Shared Haplotype Indicates a Founder Event in Unverricht–Lundborg Disease Patients from Serbia

Abstract

Unverricht-Lundborg disease (ULD) is an autosomal recessive disorder caused by dodecamer repeat expansion in the promoter region of the cystatin B (CSTB) gene in approximately 90% of the disease alleles worldwide. This study presents results of genetic findings in four Serbian unrelated patients with clinical and molecular diagnosis of ULD. Using newly established PCR protocol with betaine, we detected a homozygous expansion of dodecamer repeats in the CSTB gene in four patients with clinical diagnosis of ULD. Our results are in agreement with previous studies showing that dodecamer repeats expansion is the most common mutation associated with ULD. Haplotype analysis of eight unrelated ULD chromosomes was performed using seven markers flanking CSTB gene and one intragenic variant. We demonstrated the existence of a founder effect, strongly supported by LD calculations. Size of the minimal common haplotype implies that the most recent common ancestor of the Serbian ULD patients lived about 110 generations ago. We showed that Serbian ULD patients share the same common ancestor with patients from Baltic countries and North Africa. In the light of our data, we proposed extended minimal common haplotype, which could be considered as initial haplotype of the founder event common for Serbian, Baltic, and North African ULD patients.

GSTA1, GSTM1, GSTP1 and GSTT1 polymorphisms in progressive myoclonus epilepsy: A Serbian case–control study

“…Using PCR protocol with betaine, we amplified promoter region of the CSTB gene. After separation of amplified products in 2% agarose gel along with DNA size standard, we detected a homozygous expansion of dodecamer repeats in four ULD patients [15]. Molecular diagnostics of LD, MERRF and NCL patients was performed by sequencing coding regions of appropriate genes.…”

First Molecular Diagnosis of a Patient with Unverricht-Lundborg Disease in Korea

“…Unverricht-Lundborg disease (ULD) (EPM1, OMIM 254800) is the “purest” type and the most common form of progressive myoclonic epilepsy (PME). 1 2 It is characterized by symptoms of myoclonic jerks and generalized tonic-clonic seizures (GTCSs), which are caused by photic or touching stimulus and usually occur at the age 6–16 years. 3 This disease is an autosomal recessive disorder, and the CSTB gene encoding cystatin B, a cysteine protease inhibitor, is the only gene known to be associated with ULD.…”

Estudo molecular epilepsia mioclônica progressiva de UnverrichtLundborg (emp1) na população brasileira

“…Para todas as experiências realizadas foram utilizados um controle normal (3/3-193pb), um controle positivo (62/62-900/900pb),um portador (3/62 -193/900pb , (2, 3) portador heterozigótico para expansão, (4) alelo na faixa de tamanhos normal e (5) expansão homozigótica. Fonte Kecmanovic et al, 2014 Já no artigo de Joensuu et al, 2007 (Figura 26) foi utilizada a técnica de hibridização por Southern Blot, que consiste em utilizar sondas que emitem radiação que marcam os fragmentos de DNAs alvos e um protocolo com Kit de enzimas especificas para amplificação de longos fragmentos. Na análise dos fragmentos estudados por eletroforese em gel de agarose nós testamos várias temperaturas, sendo necessário encontrar a temperatura ideal para o estudo da região onde está a mutação, de forma que a mesma seja visualizada.…”