Coexistence of Unverricht-Lundborg disease and congenital deafness: molecular resolution of a complex comorbidity.
OBJECTIVE
We report on genetic analysis of a complex condition in a Serbian family of four siblings, wherein two had progressive myoclonic epilepsy (PME) and congenital deafness (CD), one had isolated congenital deafness (ICD), and one was healthy.


RESULTS
Molecular diagnosis performed by Southern blotting confirmed Unverricht-Lundborg disease in the available sibling with PME/CD. In the sibling with ICD (heterozygote for expansion mutation in CSTB) we demonstrated recombination event between the D21S2040 marker and the CSTB gene and identified c.207delC (p.T70Xfs) mutation in the fourth exon of the transmembrane protease, serine-3 (TMPRSS3) gene (maps in close proximity to CSTB), responsible for nonsyndromic deafness in the sibling with PME/CD as well.


CONCLUSIONS
To the best of our knowledge this is the first genetic confirmation of the coexistence of these two mutations.
Kecmanović
Miljana
M
Faculty of Biology, University of Belgrade, Belgrade, Serbia.
Ristić
Aleksandar J
AJ
Sokić
Dragoslav
D
Keckarević-Marković
Milica
M
Vojvodić
Nikola
N
Ercegovac
Marko
M
Janković
Slavko
S
Keckarević
Dusan
D
Savić-Pavićević
Dusanka
D
Romac
Stanka
S
D000293:Adolescent; D000328:Adult; D055313:Cystatin B / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D042622:DNA Repeat Expansion / Q000235:genetics; D003638:Deafness / Q000453:epidemiology* / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020191:Myoclonic Epilepsies, Progressive / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D020194:Unverricht-Lundborg Syndrome / Q000453:epidemiology* / Q000235:genetics*
C524994:CSTB protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D055313:Cystatin B; D012697:Serine Endopeptidases; C409042:TMPRSS3 protein, human