NA26651

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Muscular Dystrophies
CMD Specific
PIGI Consented Sample

Quantity

25 µg

Quantitation Method

Please see our FAQ

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

DNA from LCL

Race

White

Ethnicity

English, Irish, German, French

Country of Origin

USA

Family Member

Family History

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; asymptomatic when heart murmur was detected at age 59; dyspnea on exertion walking up flights of stairs; diffuse myalgias; premature beats shown to be PVCs in the past; dizziness when bending over and arising too fast; heart examination revealed a grade 2 medium pitched midsystolic murmer heard best along the left sternal border that increases in intensity with Valsalva's maneuver; mid cavitary obstruction; EKG showed mild sinus bradycardia; small narrow Q waves in leads V1 through V3 and larger Q waves although narrow in lead 1 and lead aVL; T wave abnormalities in leads 3 and aVF; transthoracic echocardiogram at age 62 showed for left ventricle: systolic function was vigorous; wall thickness mildly increased; ejection fraction estimated to be 70%; wall thickness mildly increased; asymmetric hypertrophy of the septum; mid cavity obliteration at rest but no significant gradient in mid cavity or LVOT; left atrium: mildly dilated; right ventricle: systolic pressure was at the upper limits of normal; estimated peak pressure was 37 mmHg; Medications: nasal pain; gabapentin; and trazodone taken at night; family history shows maternal grandfather: affected and had sympthomology; died of heart failure in mid sixties; mother affected: asymptomatic until about age 60; diagnosed with IHSS after adverse reaction to anesthesia; got dual chamber pacemaker with AV internal set to maximize CO; sister: asymptomatic until 55 years old; had myomectomy; got pacemaker; tested positive for MYH7 class 1 variant (Leu908 Val); second sister: cardiac arrest at age 14; 3 surgeries to reduce left ventricle size; heart dilated; heart transplant at age 45; symptoms started as thickened intraventricular septum with the thickest area including the bundle of HIS below aortic valve; subaortic stenosis developed blocking outflow during systole; mitral regurge heard as murmur; third sister: asymptomatic; family members not in repository; fibroblast GM26652. No genetic testing done for the proband.

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

Gene

MYH7

Chromosomal Location

14q11.2

Allelic Variant 1

160760.0010; CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC; CMH1

Identified Mutation

LEU908VAL; Fananapazir et al. (1993) found evidence, on soleus muscle biopsy, of central core disease (117000) in 10 of 13 patients with the leu908-to-val mutation. Although the mutations in the MYH7 gene were associated with skeletal muscle changes characteristic of central core disease, such was not found in patients with hypertrophic cardiomyopathy unlinked to MYH7. Notably, in 1 branch of a family with the L908V mutation, 2 adults and 3 children had histologic changes of central core disease without evidence of cardiac hypertrophy by echocardiogram. One of the adults had skeletal myopathic changes. McKenna (1993) stated that he had never seen clinical evidence of skeletal myopathy in patients with CMH1.