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 |
| Protocols |
Protocol PDF |
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Biopsy Source
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Blood
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Cell Type
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Stem cell
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Cell Subtype
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Induced pluripotent stem cell
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Transformant
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Reprogrammed (Sendai)
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Sample Source
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iPSC from Blood
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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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ISCN
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46,XX[20]
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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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| Induced Pluripotent Stem Cell |
The parental cell line was recovered reprogrammed to an induced pluripotent stem cell line and expanded. The expanded line was evaluated for viability surface antigen expression and alkaline phosphatase activity. Pluripotency was assessed via embryoid body (EB) formation. Steady-state mRNA expression patterns of undifferentiated iPSC and EBs were determined via real-time PCR. Characterization data are included in the Certificate of Analysis. |
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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) |
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| 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). Researchers purchasing hiPSCs from the NIGMS Repository are responsible for any limited use label licenses (LULLs) applicable to the cell line purchased. The applicable LULL to this line is Sendai-CytoTune. |
| 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 |
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