Direct molecular genetic diagnosis and carrier identification in one

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1.

Poster

Canki-Klain; Nina; Prof. M.D.D.Sc.

Division of Neurogenetics,

Department of Neurology

Zagreb University Medical School

10 000 Zagreb,Kišpatićeva 12

Croatia

(+ 385) 1 233 3233 ext 356

(+ 385) 1 233 5595 e-mail nina.canki-klain@zg.tel.hr

Emery-Dreifuss muscular dystrophy ; Phenotype ; Mutation identification ; Emerin

Not eligible

Not eligible

Direct molecular genetic diagnosis and carrier identification in one Emery-Dreifuss muscular dystrophy family

Canki-Klain , Nina (1) (3) ; Recan, D (2) ; Llense S (2) ; Barbot JC (2) ;Leturcq F (2)

;Deburgrave N (2) ; Kaplan JC (2) ; Debevec M (3) ; Zurak N (1)

(1)Department of Neurology, Zagreb University Medical School, Croatia, (2)

Laboratoire de Biochimie et Génétique Moléculaire,Paris, France, (3) Division of

Medical Genetics,Department of Gynecology and Obstetrics,Clinical Centre of Ljubljana

, Slovenia

Emery-Dreifuss muscular dystrophy(EMD) is an uncommon but distinctive type of muscular dystrophy with striking inter and intrafamilial clinical variability. Therefore systematic clinico-genetic correlation studies are needed to better define the X-linked phenotype, to determine the major clinical features at different ages and to precise the diagnosis in sporadic cases. We report a three-generation X-linked EMD family. The propositus,initially seen at 24 years of age had severe,very early onset clinical course.

Three affected maternal uncles died suddenly at 32, 34 and 62 respectively. His obligate carrier grand-mother died suddenly at 39 years of age. His sister was asymptomatic except ECG abnormalities. She had three children :a girl and DZ twin boys with normal early motor milestones. At 9 years,both twins had minimal clinical symptoms,moderately elevated CK and cardiac conduction defects. As no samples of the proband was available,the mutation was identified by direct sequencing of the whole EMDgene on genomic DNA of affected twins. It is a T insertion in exon 2(417 ins T) which results in a frameshift with a stop codon at position 62. The western blot, performed on lymphoblastoid cell lines, showed a total absence of emerin in both affected boys ,and normal labelled band in their sister.

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