GM28364
LCL from B-Lymphocyte
Description:
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 42; DEE42
CALCIUM CHANNEL, VOLTAGE-DEPENDENT, P/Q TYPE, ALPHA-1A SUBUNIT; CACNA1A
MANNOSIDOSIS, BETA A, LYSOSOMAL; MANSB
MANNOSIDASE, BETA A, LYSOSOMAL; MANBA
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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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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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LCL 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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Hungarian, Swedish, Irish
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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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Molecular characterization before cell line submission to CCR
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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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| Gene |
CACNA1A |
| Chromosomal Location |
19p13.13 |
| Allelic Variant 1 |
Arg>Pro; DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 42; DEE42 |
| Identified Mutation |
c.5000G>C (p.Arg1667Pro) |
| |
| Gene |
MANBA |
| Chromosomal Location |
4q24 |
| Allelic Variant 1 |
Asn578Ilefs*47; MANNOSIDOSIS, BETA A, LYSOSOMAL; MANSB |
| Identified Mutation |
c.1733del (p.Asn578Ilefs*47) |
| Demographic Data |
| Relation to Proband |
proband |
| Age at Sampling |
6 YR |
| Sex |
Female |
| Age of Onset(If not a control) |
0 YR |
| Age at Diagnosis(If not a control) |
4 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: |
WHOLE EXOME SEQUENCING ANALYSIS OF GENOMIC DNA REVEALED A DE NOVO HETEROZYGOUS AUTOSOMAL DOMINANT PATHOGENIC VARIANT (C.5000G>C) IN THE CACNA1A GENE (NM_001127221.1) RESULTING IN A MISSENSE MUTATION (P.ARG1667PRO); ALIGNED TO HUMAN GENOME BUILD GRCH37; NEXT GENERATION SEQUENCING ANALYSIS OF GENOMIC DNA REVEALED A HETEROZYGOUS AUTOSOMAL RECESSIVE PATHOGENIC VARIANT (C.1733DEL) IN THE MANBA GENE (NM_005908.3) RESULTING IN A FRAMESHIFT MUTATION (P.ASN578ILEFS*47) |
| Zygosity: |
Heterozygous |
| Other variants: |
NEXT GENERATION SEQUENCING ANALYSIS OF GENOMIC DNA ALSO REVEALED A HETEROZYGOUS AUTOSOMAL RECESSIVE VARIANT [C.987-15C>G (P.?)] OF UNKNOWN SIGNIFICANCE IN THE IQCB1 GENE (NM_001023570.2), A HETEROZYGOUS AUTOSOMAL RECESSIVE VARIANT [C.1325T>G (P.VAL442GLY)] OF UNKNOWN SIGNIFICANCE IN THE KIAA0226 GENE (NM_014687.2) AND A HETEROZYGOUS AUTOSOMAL RECESSIVE VARIANT [C.844G>A (P.GLY282SER)] OF UNKNOWN SIGNIFICANCE IN THE FA2H GENE (NM_024306.4) |
| Age of Symptom Onset and Age at Diagnosis |
| Age of Symptom Onset: |
BIRTH |
| Age at Diagnosis: |
4 YEARS OLD |
| In Utero History Information |
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| Birth History Information |
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| Dysmorphic Features |
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Strabismus
Microcephaly
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| Neurological Symptoms |
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Corpus callosum abnormalities
Ataxia
Hypotonia
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| Additional Information: |
THINNING OF THE CORPUS COLLOSUM; SMALL CEREBELLUM, BRAIN STEM, PONS AND ENLARGEMENT OF THE EXTRA AXIAL SUBARACHNOID SPACES |
| Optical and Audiological Symptoms |
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Nystagmus
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| Musculoskeletal Symptoms |
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| Developmental Milestones |
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Global developmental delay
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| Gastrointestinal Symptoms |
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| Genitourinary Symptoms |
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| Respiratory and Cardiovascular Symptoms |
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| Cognitive and Behavioral Symptoms |
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| Additional Information |
| Testing Performed |
| Neurological Testing: |
MRI - PONTOCEREBELLAR HYPOPLASIA, ATROPHY OF THE CEREBELLUM; ABNORMAL MYELINATION IN THE CEREBELLUM, WITH GLIOTIC WHITE MATTER; ATROPHY OF THE PONS; DEFICIT OF NAA IS DETECTED IN THE PONS AND SUPERIOR CEREBELLAR VERMIS |
| Musculoskeletal and Developmental Testing: |
EMG - NORMAL |
| Treatments and Assistive Devices |
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Wheelchair or ambulation devices
glasses
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| Medications |
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ACETAZOLAMIDE; GABAPENTIN |
| Family History |
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MOTHER, FATHER, AND SIBLING DO NOT CARRY THE DE NOVO MUTATION IN CACNA1A GENE |
| Remarks |
See "Phenotypic Data" Tab; unaffected mother is GM28365 (lymph); unaffected father is GM28366 (lymph). |
| Grosso BJ, Kramer AA, Tyagi S, Bennett DF, Tifft CJ, D'Souza P, Wangler MF, Macnamara EF, Meza U, Bannister RA, Complex effects on Ca Scientific reports12:9186 2022 |
| PubMed ID: 35655070 |
| Gene Cards |
CACNA1A |
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MANBA |
| Gene Ontology |
GO:0003677 DNA binding |
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GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds |
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GO:0004567 beta-mannosidase activity |
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GO:0005245 voltage-gated calcium channel activity |
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GO:0005509 calcium ion binding |
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GO:0005634 nucleus |
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GO:0005764 lysosome |
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GO:0005891 voltage-gated calcium channel complex |
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GO:0005975 carbohydrate metabolism |
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GO:0006355 regulation of transcription, DNA-dependent |
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GO:0006464 protein modification |
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GO:0006812 cation transport |
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GO:0006816 calcium ion transport |
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GO:0007204 cytosolic calcium ion concentration elevation |
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GO:0007268 synaptic transmission |
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GO:0007399 neurogenesis |
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GO:0008219 cell death |
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GO:0016021 integral to membrane |
| NCBI Gene |
Gene ID:4126 |
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Gene ID:773 |
| NCBI GTR |
248510 MANNOSIDOSIS, BETA A, LYSOSOMAL; MANSB |
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601011 CALCIUM CHANNEL, VOLTAGE-DEPENDENT, P/Q TYPE, ALPHA-1A SUBUNIT; CACNA1A |
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609489 MANNOSIDASE, BETA A, LYSOSOMAL; MANBA |
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617106 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 42; DEE42 |
| OMIM |
248510 MANNOSIDOSIS, BETA A, LYSOSOMAL; MANSB |
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601011 CALCIUM CHANNEL, VOLTAGE-DEPENDENT, P/Q TYPE, ALPHA-1A SUBUNIT; CACNA1A |
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609489 MANNOSIDASE, BETA A, LYSOSOMAL; MANBA |
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617106 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 42; DEE42 |
| Split Ratio |
1:4 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Roswell Park Memorial Institute Medium 1640 with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not Inactivated |
| Substrate |
None specified |
| Subcultivation Method |
dilution - add fresh medium |
| Supplement |
- |
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