GM25950

GM25950 Fibroblast

Description:

MYOPATHY, CENTRONUCLEAR, 1; CNM1
TITIN; TTN

Affected:

Yes

Sex:

Male

Age:

8 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
CMD Specific
PIGI Consented Sample

Biopsy Source

Back

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Ethnicity

Not Hispanic/Latino

Country of Origin

USA

Family History

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; symptom onset during first 6 months of life; presentation in utero with decreased fetal movements, muscle weakness/decreased respiration at birth; facial weakness; high-arched palate; scoliosis; maximum motor function ever achieved: sit when placed; current motor function: sit when placed; motor functions never achieved: holding head up without assistance, walking without assistance, or running; normal cognitive ability; diagnosis of centronuclear myopathy confirmed by muscle biopsy, skin biopsy, and genetic testing; myopathic nerve conduction velocity; myopathic EMG; absent deep tendon reflexes; biopsy at 3 months of age revealed central nuclei and fiber size variation but no type I fiber predominance and no increase in connective tissue or endomysial tissue; Sanger sequencing revealed compound heterozygous mutation in the TTN gene: c.15721+1G>A (full-length titin, NM_001267550.1) on intron 52 of the paternal allele - a predicted splice site variant, c.44998_45001del and c.106244delG frameshift mutations on the maternal allele; normal MRI/CT scan; normal echo; no ocular, cardiac or brain involvement; management: at 5 years, needed pulmonary aspiration and used oxygen support during the day, had combined oral and G-tube feeding since infancy; no trach tube; no family history of disease; subject is 979-1 in Neurology (2013) 81:1-10, PMID:23975875.

Characterizations

PDL at Freeze

4.9

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

Gene

TTN

Chromosomal Location

2q31.2

Allelic Variant 1

; MYOPATHY, CENTRONUCLEAR

Identified Mutation

c.15721+1G>A; Titin

Gene

TTN

Chromosomal Location

2q31.2

Allelic Variant 2

; MYOPATHY, CENTRONUCLEAR

Identified Mutation

c.44998_45001del (p.N22897fs)

Gene

TTN

Chromosomal Location

2q31.2

Allelic Variant 2

; MYOPATHY, CENTRONUCLEAR

Identified Mutation

c.106244delG (p.G32772fs)

Phenotypic Data

Demographic Data

Relation to Proband

proband

Age at Sampling

8 YR

Sex

Male

Age of Onset(If not a control)

6 MO

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:

TTN, C.15721+G>A, SPLICING, INTRON 52

Zygosity:

Heterozygous

Other variants:

TTN, C.44998_45001DEL (P.N22897FS), FRAMESHIFT, EXON 326 TTN, C.106244DELG (P.G32772FS), FRAMESHIFT, EXON 358

Age of Symptom Onset and Age at Diagnosis

Age of Symptom Onset:

6 MONTHS

In Utero History Information

Decreased fetal movement

Birth History Information

Additional Information:

MUSCLE WEAKNESS DECREASED RESPIRATION

Dysmorphic Features

Neurological Symptoms

Optical and Audiological Symptoms

Musculoskeletal Symptoms

Developmental Milestones

Holding Head Up Without Assistance:

Not achieved and not maintained

Sitting Without Assistance:

Achieved and maintained

Walking Without Assistance:

Not achieved and not maintained

Running:

Not achieved and not maintained

Gastrointestinal Symptoms

Additional Information:

COMBINED ORAL AND G-TUBE FEEDING

Genitourinary Symptoms

Respiratory and Cardiovascular Symptoms

Additional Information:

PULMONARY ASPIRATION

Cognitive and Behavioral Symptoms

Additional Information

Testing Performed

Neurological Testing:

NERVE CONDUCTION VELOCITY: MYOPATHIC ELECTROMYOGRAPHY: MYOPATHIC DEEP TENDON REFLEXES: ABSENT MRI: NORMAL

Musculoskeletal and Developmental Testing:

MUSCLE BIOPSY: CENTRAL NUCLEI, FIBER SIZE VARIATION

Treatments and Assistive Devices

Additional Testing:

USE RESPIRATORY SUPPORT ALL NIGHTS, WHEN ILL OR IN ANTICIPATION OF SURGERY

Medications

Family History

Remarks

Publications

Ceyhan-Birsoy O, Agrawal PB, Hidalgo C, Schmitz-Abe K, DeChene ET, Swanson LC, Soemedi R, Vasli N, Iannaccone ST, Shieh PB, Shur N, Dennison JM, Lawlor MW, Laporte J, Markianos K, Fairbrother WG, Granzier H, Beggs AH, Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy Neurology81:1205-14 2013

PubMed ID: 23975875