HM23417
High Molecular Weight DNA from B-Lymphocyte
Description:
MYOPATHY, CENTRONUCLEAR, 1; CNM1
MYOPATHY, PROXIMAL, WITH EARLY RESPIRATORY MUSCLE INVOLVEMENT; MPRM
TITIN; TTN
GAP JUNCTION PROTEIN, BETA-2; GJB2 (CONNEXIN 26; CX26)
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Muscular Dystrophies
CMD Specific |
| Class |
Congenital Muscle Diseases |
| Estimated Quantity |
5 µg - 20 µg |
| Product Specifications |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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High Molecular Weight DNA from B-Lymphocyte
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Race
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White
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Ethnicity
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Not Hispanic/Latino
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Ethnicity
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POLISH/IRISH/ENGLISH
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Country of Origin
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USA
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Family Member
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1
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Family History
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N
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
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| Gene |
TTN |
| Chromosomal Location |
2q31.2 |
| Allelic Variant 1 |
VAL10952LEU; CENTRONUCLEAR MYOPATHY 1 |
| Identified Mutation |
32854 G>C; Titin, or connectin, is a giant muscle protein expressed in the cardiac and skeletal muscles that spans half of the sarcomere from Z line to M line. Titin plays a key role in muscle assembly, force transmission at the Z line, and maintenance of resting tension in the I band region (Itoh-Satoh et al., 2002). |
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| Gene |
TTN |
| Chromosomal Location |
2q31.2 |
| Allelic Variant 1 |
VAL10952LEU; CENTRONUCLEAR MYOPATHY 1 |
| Identified Mutation |
32854 G>C; Titin, or connectin, is a giant muscle protein expressed in the cardiac and skeletal muscles that spans half of the sarcomere from Z line to M line. Titin plays a key role in muscle assembly, force transmission at the Z line, and maintenance of resting tension in the I band region (Itoh-Satoh et al., 2002). |
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| Gene |
TTN |
| Chromosomal Location |
2q31.2 |
| Allelic Variant 2 |
; CENTRONUCLEAR MYOPATHY 1 |
| Identified Mutation |
37112-1G>A (IVS191-1G>A); Titin, or connectin, is a giant muscle protein expressed in the cardiac and skeletal muscles that spans half of the sarcomere from Z line to M line. Titin plays a key role in muscle assembly, force transmission at the Z line, and maintenance of resting tension in the I band region (Itoh-Satoh et al., 2002). |
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| Gene |
TTN |
| Chromosomal Location |
2q31.2 |
| Allelic Variant 2 |
; CENTRONUCLEAR MYOPATHY 1 |
| Identified Mutation |
37112-1G>A (IVS191-1G>A); Titin, or connectin, is a giant muscle protein expressed in the cardiac and skeletal muscles that spans half of the sarcomere from Z line to M line. Titin plays a key role in muscle assembly, force transmission at the Z line, and maintenance of resting tension in the I band region (Itoh-Satoh et al., 2002). |
| Remarks |
Clinically affected; Centronuclear myopathy and connexin 26 hearing loss; born full term via normal spontaneous delivery; birth weight 6lb 9 oz; apgar scores: 9 at 1 min and 9 at 5 min; failed initial newborn hearing screening but passed repeat test several weeks later; hyporeflexia and hypotonia onset at 2 months of age; head lag and developmental delay noted at 5 months due to severe weakness of neck muscles; weakness of arms, legs; scoliosis; physical exam at 11 years 6 months: subject noted to be ambulant but had difficulty lifting head or torso against gravity and fatigued easily, had decreased vital capacity, facial weakness, and absent deep tendon reflexes; developmental milestones achieved and maintained through age 11: sat at 9 months, held head up and turned in bed at 12 months, stood at 14 months, walked indoors at 16 months, and walked outdoors at 18 months; climbed stairs with a handrail at 24 months; ran (feet leaving ground) at 5 years; Muscle biopsy at age 14 months: revealed marked increase in the number of fibers with internal and central nuclei, fiber size variation, Type I fiber predominance, and increase in connective or endomysial tissue; electron micrograph of muscle biopsy revealed: disintegrated sarcomeres showing disrupted I- and A-band regions; indirect immunofluorescence analysis of the muscle biopsy indicated normal sarcomere labeling with the titin N-terminal and A-I junction antibodies (titin integrated into sarcomeres and structure intact up to A-I junction), but there was complete loss at the C-terminal of titin which contains a binding site for calpain 3 (CAPN3); immunostaining for CAPN3 indicated a loss of the CAPN3 binding region on the mutant titin proteins; reduced immunostaining for AldoA receptors indicated that the mutations lie in the titin N2-line region; whole exome sequencing was performed (UCSC hg19); subject is a compound heterozygote for the following mutations in the TTN gene; mutation 1 (paternal) in exon 168: p.Val10952Leu (GTT>CTT), c.32854G>C; mutation 2 (maternal) intron 191: c.37112-1G>A, IVS191-1 G>A; audiology evaluation at age 5: mild sensorineural hearing loss on the left side; repeat audiological evaluations every six months revealed progressive hearing loss, L>R; audiological exam at age 8 years: mild sensorineural hearing loss 250-1500 Hz rising within normal limits through 8000 Hz in right ear and a mild sloping to a moderately severe sensorineural hearing loss 250-2000 Hz rising to within normal limits through 8000 Hz in left ear, middle ear muscle reflexes absent to contralateral stimulation 500-2000 Hz, stimulating either ear, distortion-product otoacoustic emissions were consistent with a low to mid frequency hearing loss; word recognition excellent bilaterally; excellent speech perception at average conversation levels (50 dB); Connexin 26 GJB2 gene sequencing revealed subject is heterozygous for 342kb deletion (35delG) and heterozygous for an M34T change, which was reported to be sufficient to result in significant hearing loss when inherited in combination with 35delG in 2007 at the time of testing; subject uses Widex Inteo SD-9M post auricular hearing aids; subject uses breathing support at night or when ill; carrier mother has mild subclinical cardiac and skeletal myopathy, no other family history of centronuclear myopathy or connexin 26 hearing loss; subject fibroblast cell line is GM25936; carrier mother is GM25951 (lymphoblast), unaffected carrier father is GM25948 (lymphoblast), and maternal grandmother is GM25993 (lymphoblast); subject is 314-1 in Neurology (2013) 81:1205-14, PMID:23975875. |
| 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 |
| Gene Cards |
GJB2 |
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TTN |
| Gene Ontology |
GO:0004601 peroxidase activity |
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GO:0004674 protein serine/threonine kinase activity |
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GO:0004713 protein-tyrosine kinase activity |
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GO:0004896 hematopoietin/interferon-class (D200-domain) cytokine receptor activity |
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GO:0005524 ATP binding |
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GO:0005856 cytoskeleton |
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GO:0005886 plasma membrane |
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GO:0005922 connexon complex |
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GO:0005975 carbohydrate metabolism |
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GO:0006468 protein amino acid phosphorylation |
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GO:0006810 transport |
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GO:0006941 striated muscle contraction |
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GO:0006942 regulation of striated muscle contraction |
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GO:0006979 response to oxidative stress |
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GO:0007267 cell-cell signaling |
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GO:0007517 muscle development |
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GO:0007605 perception of sound |
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GO:0008307 structural constituent of muscle |
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GO:0015285 connexon channel activity |
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GO:0016020 membrane |
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GO:0016021 integral to membrane |
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GO:0017022 myosin binding |
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GO:0030017 sarcomere |
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GO:0030018 Z disc |
| NCBI Gene |
Gene ID:2706 |
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Gene ID:50981 |
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Gene ID:7273 |
| NCBI GTR |
121011 GAP JUNCTION PROTEIN, BETA-2; GJB2 |
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160150 MYOPATHY, CENTRONUCLEAR, 1; CNM1 |
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188840 TITIN; TTN |
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603689 MYOPATHY, MYOFIBRILLAR, 9, WITH EARLY RESPIRATORY FAILURE; MFM9 |
| OMIM |
121011 GAP JUNCTION PROTEIN, BETA-2; GJB2 |
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160150 MYOPATHY, CENTRONUCLEAR, 1; CNM1 |
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188840 TITIN; TTN |
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603689 MYOPATHY, MYOFIBRILLAR, 9, WITH EARLY RESPIRATORY FAILURE; MFM9 |
| Omim Description |
MYOPATHY, CENTRONUCLEAR |
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MYOTUBULAR MYOPATHY |
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