GM28756
LCL from B-Lymphocyte
Description:
CEREBRAL CREATINE DEFICIENCY SYNDROME 2; CCDS2
GUANIDINOACETATE METHYLTRANSFERASE; GAMT
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| 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
|
White
|
|
Subject Type
|
parent(s) and child(ren)
|
|
Ethnicity
|
Not Hispanic/Latino
|
|
Ethnicity
|
U.K.
|
|
Country of Origin
|
USA
|
|
Family Member
|
1
|
|
Family History
|
Y
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Molecular characterization before cell line submission to CCR
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| Gene |
GAMT |
| Chromosomal Location |
19p13.3 |
| Allelic Variant 1 |
p.V78E; CEREBRAL CREATINE DEFICIENCY SYNDROME 2; CCDS2 |
| Identified Mutation |
c.233T>A |
| |
| Gene |
GAMT |
| Chromosomal Location |
19p13.3 |
| Allelic Variant 2 |
R105GfsX26; CEREBRAL CREATINE DEFICIENCY SYNDROME 2; CCDS2 |
| Identified Mutation |
c.299_c.311 dup13 |
| Demographic Data |
| Relation to Proband |
proband |
| Age at Sampling |
18 YR |
| Sex |
Female |
| Age of Onset(If not a control) |
1 YR |
| Age at Diagnosis(If not a control) |
5 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: |
GAMT, C.299_C.311DUP13 (P.R105G1AX2B), EXON 2 |
| Zygosity: |
Compound Heterozygous |
| Other variants: |
GAMT, C.233T>A (P. V78E), EXON 2 |
| Age of Symptom Onset and Age at Diagnosis |
| Age of Symptom Onset: |
1 YEAR |
| Age at Diagnosis: |
5 YEARS |
| In Utero History Information |
| |
|
| Birth History Information |
| |
|
| Dysmorphic Features |
| |
|
| Neurological Symptoms |
| |
Seizures
|
| Additional Information: |
SEIZURES BEGAN AGE 5 WITH ABSENCE EPILEPSY AND GENERALIZED TONIC-CLONIC EPISODES BEGINNING AT AGE 10. |
| Optical and Audiological Symptoms |
| |
|
| Musculoskeletal Symptoms |
| |
|
| Developmental Milestones |
| |
Delayed speech and language development
Global developmental delay
|
| Additional Information: |
ACADEMIC DELAYS |
| Gastrointestinal Symptoms |
| |
|
| Genitourinary Symptoms |
| |
|
| Respiratory and Cardiovascular Symptoms |
| |
|
| Cognitive and Behavioral Symptoms |
| |
Behavioral problems
Learning disability
|
| Intellectual Disability: |
Moderate |
| Additional Information: |
CLINICALLY PROBLEMS WITH INHIBITION, EMOTIONAL CONTROL, PLANNING/ORGANIZATION, SELF-MONITORING, ATYPICALITY, WITHDRAWAL, AND FUNCTIONAL COMMUNICATIONS. DEFICITS IN ADAPTIVE FUNCTIONING AND DAILY FUNCTIONING SKILLS; POSITIVE EMOTIONAL AND BEHAVIORAL ADJUSTMENT. |
| Additional Information |
| Uncategorized Symptoms: |
EUTHYMIC MOOD AND ALERT; SIGNIFICANT COGNITIVE SLOWING; LIMITED RECEPTIVE AND EXPRESSIVE LANGUAGE SKILLS WITH LIMITED VOCABULARY DEVELOPMENT; ARTICULATE AND INTELLIGIBLE SPEECH. |
| Testing Performed |
| Cognitive and Behavioral Testing: |
WECHSLER INTELLIGENCE SCALE FOR CHILDREN; BEHAVIOR ASSESSMENT SYSTEM FOR CHILDREN; BEHAVIOR RATING INVENTORY OF EXECUTIVE FUNCTION (BRIEF).
VERBAL COMPREHENSION (45) EXTREMELY LOW; VISUAL SPATIAL (45) EXTREMELY LOW; FLUID REASONING (61) EXTREMELY LOW; WORKING MEMORY (59) EXTREMELY LOW; PROCESSING SPEED (56) EXTREMELY LOW. |
| Treatments and Assistive Devices |
| |
Speech therapy
Communication or learning devices
|
| Surgeries |
LITHOTRIPSY, VAGAL NERVE STIMULATION, TOTAL SHOULDER ARTHROPASTY. |
| Medications |
| |
LAMICTAL, ONFI. |
| Family History |
| |
YOUNGER BROTHER IS CURRENTLY ASYMPTOMATIC DUE TO EARLY DIAGNOSIS AND TREATMENT. |
| Remarks |
Clinically affected. Substantial developmental delay, moderate intellectual disability, and mild epilepsy. Patient 2 of Viau 2013 (PMID: 24071436). Patient 25 of Stockler-Ipsiroglu (PMID: 24268530). Assessed for developmental disabilities at 3 years of age. Seizures began at 5 years of age. Treatment began at 5 years and 6 months of age for 30 months; improvement on developmental delay, speech delay and behavior, remaining mild epilepsy. Brother GM28757 is currently asymptomatic after early diagnosis and treatment. Mother is GM28759. Father is GM28758. Fibroblast line is GM28379 and iPSC line is GM28936. |
| Stockler-Ipsiroglu S, van Karnebeek C, Longo N, Korenke GC, Mercimek-Mahmutoglu S, Marquart I, Barshop B, Grolik C, Schlune A, Angle B, Araújo HC, Coskun T, Diogo L, Geraghty M, Haliloglu G, Konstantopoulou V, Leuzzi V, Levtova A, Mackenzie J, Maranda B, Mhanni AA, Mitchell G, Morris A, Newlove T, Renaud D, Scaglia F, Valayannopoulos V, van Spronsen FJ, Verbruggen KT, Yuskiv N, Nyhan W, Schulze A, Guanidinoacetate methyltransferase (GAMT) deficiency: outcomes in 48 individuals and recommendations for diagnosis, treatment and monitoring Molecular genetics and metabolism111:16-25 2013 |
| PubMed ID: 24268530 |
| |
| Viau KS, Ernst SL, Pasquali M, Botto LD, Hedlund G, Longo N, Evidence-based treatment of guanidinoacetate methyltransferase (GAMT) deficiency Molecular genetics and metabolism110:255-62 2013 |
| PubMed ID: 24071436 |
| Split Ratio |
1:6 |
| 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 |
- |
|