GM26045
Fibroblast from Skin, Thigh
Description:
RIGIDITY AND MULTIFOCAL SEIZURE SYNDROME, LETHAL NEONATAL; RMFSL
BRCA1-ASSOCIATED ATM ACTIVATOR 1; BRAT1
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
PIGI Consented Sample |
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Biopsy Source
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Thigh
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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Transformant
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Untransformed
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Sample Source
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Fibroblast from Skin, Thigh
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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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Amish
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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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Y
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Relation to Proband
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proband
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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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| PDL at Freeze |
3.03 |
| Passage Frozen |
2 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
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| Gene |
BRAT1 |
| Chromosomal Location |
7p22.3 |
| Allelic Variant 1 |
614506.0001; RIGIDITY AND MULTIFOCAL SEIZURE SYNDROME, LETHAL NEONATAL |
| Identified Mutation |
c.638_639insA; By homozygosity mapping followed by exome sequencing of 2 Amish patients from Pennsylvania with lethal neonatal rigidity and multifocal seizure syndrome (RMFSL; 614498), Puffenberger et al. (2012) identified a homozygous 1-bp insertion (638_639insA) in the BRAT1 gene, resulting in a frameshift and premature termination. Two unrelated Old Order Amish infants from different demes in Wisconsin and Kentucky with a similar phenotype were found to carry the same homozygous mutation. Two heterozygous carriers of this mutation were found among 201 Old Order Amish control samples, yielding a population-specific allele frequency of 0.50%. The mutation abolished the nuclear localization signal, and rendered the protein unstable when expressed in human cells as shown by Western blot analysis. |
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| Gene |
BRAT1 |
| Chromosomal Location |
7p22.3 |
| Allelic Variant 2 |
614506.0001; RIGIDITY AND MULTIFOCAL SEIZURE SYNDROME, LETHAL NEONATAL |
| Identified Mutation |
c.638_639insA; By homozygosity mapping followed by exome sequencing of 2 Amish patients from Pennsylvania with lethal neonatal rigidity and multifocal seizure syndrome (RMFSL; 614498), Puffenberger et al. (2012) identified a homozygous 1-bp insertion (638_639insA) in the BRAT1 gene, resulting in a frameshift and premature termination. Two unrelated Old Order Amish infants from different demes in Wisconsin and Kentucky with a similar phenotype were found to carry the same homozygous mutation. Two heterozygous carriers of this mutation were found among 201 Old Order Amish control samples, yielding a population-specific allele frequency of 0.50%. The mutation abolished the nuclear localization signal, and rendered the protein unstable when expressed in human cells as shown by Western blot analysis. |
| Remarks |
Clinically affected; subject passed during same year of birth; born at 38 3/7 weeks; mother noticed unusual rhythmic, repetitive movements in utero; made first sound at 3.5 hours of life; unable to latch; bottle fed; small chest; seizures; rigidity; physical examination at 3 days of age revealed an alert, content WN/WD baby; head - microcephaly, AF nonpalpable, overriding sutures with frontal bones lower and bitemporal narrowing; eyes - RR B, upslanting palpebral fissures; ears - TM translucent B; nose - clear, flattened nasal bridge; normal mouth; high arched palate; thin lips; normal neck, respiratory, cardiovascular, abdominal, gastrourinary, extremities, hips, and back; neuro - increased tone on all extremities, tremors, cortical thumbs, scissoring; skin - erythematous macular rash, some with white papules; genetic testing by PCR using DNA isolated from peripheral blood revealed a homozygous recessive 1-bp insertion mutation in the BRAT1 gene: c.638_639insA resulting in a frameshift and premature termination (p.Val214Glyfs); medication: clonazepam; family history: older male sibling had seizures and was admitted to the hospital at 28 days of life with possible mitochondrial or liver dysfunction - based on labs with concern for fatty acid oxidation defect, but normal chromosomes; sibling died at 7 weeks of age. |
| Cumulative PDL at Freeze |
5.9 |
| Passage Frozen |
2 |
| Split Ratio |
1:4 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| Medium |
Eagles Minimum Essential Medium with Earle's salts:Dulbecco's modified MEM with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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