GM26652

GM26652 Fibroblast

Description:

CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 1; CMH1
MYOSIN, HEAVY CHAIN 7, CARDIAC MUSCLE, BETA; MYH7

Affected:

Yes

Sex:

Female

Age:

63 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Muscular Dystrophies
CMD Specific
PIGI Consented Sample

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Race

White

Ethnicity

Not Hispanic/Latino

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 member samples not in repository; lymphoblast GM26651. No genetic testing done for the proband.

Characterizations

PDL at Freeze

5.68

Passage Frozen

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.

Phenotypic Data

Demographic Data

Relation to Proband

proband

Age at Sampling

63 YR

Sex

Female

Age of Onset(If not a control)

59 YR

Age at Diagnosis(If not a control)

62 YR

Hispanic or Latino/Not Hispanic or Latino

Not Hispanic/Latino

Racial Category

White

Country

USA

Data Elements

Clinical Element Type: General NIGMS Catalog Remarks

(Baseline)

Mutation Information

Gene, variant, consequence, and exon number:

MYH7, C.2722C>G (P.LEU908VAL), MISSENSE, INFERRED FROM A FAMILY MEMBER

Zygosity:

Heterozygous

Age of Symptom Onset and Age at Diagnosis

Age of Symptom Onset:

59 YEARS

Age at Diagnosis:

62 YEARS

In Utero History Information

Birth History Information

Dysmorphic Features

Neurological Symptoms

Optical and Audiological Symptoms

Musculoskeletal Symptoms

Developmental Milestones

Gastrointestinal Symptoms

Genitourinary Symptoms

Respiratory and Cardiovascular Symptoms

Heart murmur

Additional Information:

DYSPNEA ON EXERTION WALKING UP STAIRS. OCCASIONAL SKIPPED BEATS/PREMATURE VENTRICULAR CONTRACTIONS. ASYMMETRIC SEPTAL HYPERTROPHY. MID CAVITARY OBLITERATION OF THE LEFT VENTRICLE. MILD TRICUSPID REGURGITATION WITH A LEFT VENTRICULAR SYSTOLIC PRESSURE 37 MMHG. MILD LEFT ATRIAL ENLARGEMENT. NO OBSTRUCTION OF LEFT VENTRICULAR OUTFLOW TRACT AT BASELINE. EDEMA IN FEET AND TIGHTNESS IN CALVES WITH WALKING. DIFFUSE MYALGIAS. VENTRICULAR EJECTION FRACTION AT 70%.

Cognitive and Behavioral Symptoms

Additional Information

Testing Performed

Respiratory and Cardiovascular Testing:

TRANSTHORACIC ECHOCARDIOGRAM: INITIALLY DIAGNOSED WITH HYPERTROPHIC NONOBSTRUCTIVE CARDIOMYOPATHY; SECOND ECHOCARDIOGRAPHIC TESTING INDICATED HYPERTROPHIC CARDIOMYOPATHY WITH MID CAVITARY OBSTRUCTION EKG: SINUS BRADYCARDIA GRADE 2 MEDIUM PITCHED MIDSYSTOLIC MURMUR AT THE LEFT STERNAL BORDER

Metabolic, Hematologic, and Endocrinologic Testing:

SERUM CALCIUM: 10.7 MG/DL (HIGH)

Treatments and Assistive Devices

Medications

MEDICATION FOR NASAL PAIN, GABAPENTIN, AND TRAZADONE TAKEN AT NIGHT.

Family History

MATERNAL GRANDFATHER: HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY, DIED OF HEART FAILURE IN HIS MID-60S MOTHER: DIAGNOSED WITH IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS AT 60, EVENTUALLY GOT DUAL CHAMBER PACEMAKER SISTER I: ASYMPTOMATIC UNTIL 55. HAD MYOMECTOMY; GOT PACEMAKER; MYH7 LEU908VAL VARIANT SISTER II: CARDIAC ARREST AT AGE 14; 3 SURGERIES TO REDUCE LEFT VENTRICLE SIZE; HEART EVENTUALLY DILATED AND HAD HEART TRANSPLANT AT 45; SYMPTOMS- "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."

Remarks