Lamin A/C Gene Mutation Associated With Dilated Cardiomyopathy With

Variable Skeletal Muscle Involvement

HEART…..??

Cardiomyopathy…

• Hereditory disease of heart muscle• Hard to deliver blood to the body• Leads to heart failure • Symptoms ::; breathlessness ,swellon legs,

bloated belly.• Treatments::; drugs ,implanted devices, surgery,

transplant.

There are 4 main types of cardiomyopathy.

• Dilated Cardiomyopathy.• Hypertrophic Cardiomyopathy.• Restrictive Cardiomyopathy.• Ischemic cardiomyopathy.

Dilated Cardiomyopathy…..

• Dilated cardiomyopathy (DCM) is a condition in which the heart's ability to pump blood is decreased because the heart's main pumping chamber, the left ventricle, is enlarged and weakened. In some cases, it prevents the heart from relaxing and filling with blood as it should.

• Molecular genetic studies identified of 11 candidate disease loci for inherited DCM. Only 4 disease genes responsible for DCM have been identified.

• they are Cardiac actin , Dystrophin, Tafazzin , Desmin.

k

Lamin A/C Gene

Methods..Subject.. * 14 members of the MDDC 1 family were examined . * patients were evaluated by history ,physical

examination ,ECG, echocardiography. * subject II-1 and subject II-5 underwent cardiac

catheterization, including ventriculography, coronary angiography, and endomyography biospy.

* DCM status was classified as affected , unaffected and unknown.

Lamin A/C Mutation analysis

• Coding regions of the Lamin A/C gene from patient II-1 were sequenced.

• Exon 6 were amphilified from genomic DNA isolated from MDDC 1 family.

• The resulting PCR amplimers were sequenced in both directions.

• SSCP and HDX analysis was performed.

Result….

• 14 members of the MDDC 1 family were examined, 5 of these individuals were classified as affected.

• Patient II-5 displayed a pure DCM phenotype • Patient II-1,III-3 and III-4 had mild skeletal

muscle involvement • And mild proximal limb gridle muscle weakness.

Abnormal cardiac muscle

Normal skeletal muscle Normal cardiac muscle

Skelatal muscle involvement

• Muscle pathology indicates mild dystrophic changes in patients II-1,III-3,and III-4.

• Patient II-5 was classified as pure DCM.• Patients II-1 and III-3 displayed symptoms of

LGMD, patient III- 4 displayed symptoms of EDMD.