GM28788
LCL from B-Lymphocyte
Description:
CEREBRAL CREATINE DEFICIENCY SYNDROME 1; CCDS1
SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, CREATINE), MEMBER 8; SLC6A8
Repository
|
NIGMS Human Genetic Cell Repository
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Subcollection |
Heritable Diseases PIGI Consented Sample |
Biopsy Source
|
Peripheral vein
|
Cell Type
|
B-Lymphocyte
|
Tissue Type
|
Blood
|
Transformant
|
Epstein-Barr Virus
|
Sample Source
|
LCL from B-Lymphocyte
|
Race
|
Asian
|
Subject Type
|
trio
|
Ethnicity
|
Not Hispanic/Latino
|
Ethnicity
|
Korean
|
Country of Origin
|
USA
|
Family Member
|
1
|
Family History
|
N
|
Relation to Proband
|
proband
|
Confirmation
|
Molecular characterization before cell line submission to CCR
|
Species
|
Homo sapiens
|
Common Name
|
Human
|
Remarks
|
|
Gene |
SLC6A8 |
Chromosomal Location |
Xq28 |
Allelic Variant 1 |
300036.0010; CEREBRAL CREATINE DEFICIENCY SYNDROME 1; CCDS1 |
Identified Mutation |
c.1006_1008delAAC (p.Asn336del); In a 6-year-old boy with creatine deficiency syndrome (300352), Clark et al. (2006) identified a hemizygous 3-bp deletion (1006delAAC) in exon 6 of the SLC6A8 gene, resulting in a deletion of a highly conserved residue asn336. The patient had moderate mental retardation, attention deficit-hyperactivity disorder, microcephaly, and tall stature.
Battini et al. (2007) identified the 1006delAAC mutation in a 9.5-year-old Italian boy with mental retardation and verbal dyspraxia. He had delayed psychomotor development, hypotonia, seizures, and severe language deficit with oral-motor dyspraxia, irritability, and temper tantrums. Detailed language evaluation showed problems in picture naming and phonetics, whereas receptive vocabulary was less severely affected. Social interaction was good despite the severe expressive limitation. Battini et al. (2007) noted that the phenotype in their patient was different than that reported by Clark et al. (2006). |
|
Gene |
PAH |
Chromosomal Location |
12q24.1 |
Allelic Variant 1 |
261600.0019; Hyperphenylalaninemia, non-PKU mild |
Identified Mutation |
c.1068C>A (p.Tyr356*); The tyr356-to-ter (Y356X) mutation in exon 11 of PAH was found on haplotypes 4, 7, and 9 in Chinese patients with phenylketonuria (PKU; 261600) (Wang and Woo, 1990). Also see Wang et al. (1992). This Y356X mutation is associated with multiple haplotypes, possibly due to crossover, gene conversion, or recurrent mutation. |
Demographic Data |
Relation to Proband |
proband |
Age at Sampling |
30 MO |
Sex |
Male |
Age of Onset(If not a control) |
18 MO |
Age at Diagnosis(If not a control) |
2 YR |
Hispanic or Latino/Not Hispanic or Latino |
Not Hispanic/Latino |
Racial Category |
Asian |
Country |
USA |
|
Data Elements |
Clinical Element Type: General NIGMS Catalog Remarks |
(Baseline) |
Mutation Information |
Gene, variant, consequence, and exon number: |
SLC6A8, C.1006_1008DEL (P.ASN336DEL), DELETION, EXON 6 |
Zygosity: |
Hemizygous |
Other variants: |
PAH, C.1068C>A, P.TYR356*, NONSENSE, HETEROZYGOUS, EXON 11 |
Age of Symptom Onset and Age at Diagnosis |
Age of Symptom Onset: |
18 MONTHS |
Age at Diagnosis: |
2 YEARS AND 4 MONTHS |
In Utero History Information |
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Birth History Information |
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Dysmorphic Features |
|
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Neurological Symptoms |
|
Corpus callosum abnormalities Hypotonia White matter issues
|
Additional Information: |
SENSORY PROCESSING DISORDER |
Optical and Audiological Symptoms |
|
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Musculoskeletal Symptoms |
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Developmental Milestones |
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Delayed speech and language development Global developmental delay Delayed fine motor skills Delayed gross motor skills
|
Additional Information: |
SOCIAL DELAYS |
Gastrointestinal Symptoms |
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Genitourinary Symptoms |
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Respiratory and Cardiovascular Symptoms |
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Cognitive and Behavioral Symptoms |
|
Autism spectrum disorder
|
Additional Information |
Testing Performed |
Neurological Testing: |
SV-MRS: CREATINE SIGNIFICANTLY REDUCED TO ~25% OF NORMAL; MYO-INOSITOL BORDERLINE ELEVATED; MRI: PATCHY T2/FLAIR HYPERINTENSITY IN THE PERIVENTRICULAR AND DEEP WHITE MATTER WITH ASSOCIATED MILD WHITE MATTER VOLUME LOSS AND THINNING OF THE CORPUS CALLOSUM |
Treatments and Assistive Devices |
|
Occupational therapy Physical therapy Speech therapy music therapy
|
Additional Testing: |
APPLIED BEHAVIOR THERAPY |
Medications |
Family History |
Remarks |
Clinically affected. See "Phenotypic Data" tab. |
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 |
20% fetal bovine serum Not Inactivated |
Substrate |
None specified |
Subcultivation Method |
dilution - add fresh medium |
Supplement |
- |
|