GM28075

GM28075 LCL from B-Lymphocyte

Description:

CEREBRAL CREATINE DEFICIENCY SYNDROME 1; CCDS1
SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, CREATINE), MEMBER 8; SLC6A8

Affected:

Yes

Sex:

Male

Age:

10 YR (At Sampling)

Overview

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

Ethnicity

Not Hispanic/Latino

Country of Origin

USA

Family Member

Family History

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; See "Phenotypic Data" tab; unaffected carrier mother is GM28076 (lymph).

Characterizations

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).

Phenotypic Data

Demographic Data

Relation to Proband

proband

Age at Sampling

10 YR

Sex

Male

Age of Onset(If not a control)

1 YR

Age at Diagnosis(If not a control)

7 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:

A COMPREHENSIVE EPILEPSY PANEL SEQUENCING ANALYSIS OF GENOMIC DNA REVEALED A PATHOGENIC VARIANT (C.1006_1008DELAAC) IN EXON 6 OF THE SLC6A8 GENE (NM_005629.3) RESULTING IN A DELETION MUTATION (P.ASN336DEL)

Zygosity:

Hemizygous
Notes: HEMIZYGOUS FOR X-LINKED DISORDER

Other variants:

A COMPREHENSIVE EPILEPSY PANEL SEQUENCING ANALYSIS OF GENOME DNA ALSO REVEALED A NOVEL X-LINKED HEMIZYGOUS MUTATION OF UNCERTAIN SIGNIFICANCE (C.441_455DUP15) IN EXON 2 OF THE ARX GENE (NM_139058.2) RESULTING IN A DUPLICATION MUTATION (P.ALA151_ALA155DUP) AS WELL AS A HETEROZYGOUS VARIANT (C.3428A>G) IN THE POLG GENE (P.GLU1143GLY); PCR TEST OF ISOLATED DNA WAS NEGATIVE FOR FRAGILE X EXPANSION MUTATION IN THE FMR1 GENE (<45 REPEATS); ARRAY-CGH ANALYSIS OF DNA REVEALED AN UNCLEAR CLINICALLY SIGNIFICANT ABNORMALITY INDICATING A DUPLICATION BETWEEN 63.84 AND 84.15 KB AT THE LOCUS 9Q31.2, WHICH IS A COPY GAIN BUT NO DELETION OR ABSENCE OF HETEROZYGOSITY, DUPLICATION INVOLVES FSD1L AND FKTN GENES

Age of Symptom Onset and Age at Diagnosis

Age of Symptom Onset:

1 YEAR

Age at Diagnosis:

7 YEARS

In Utero History Information

Birth History Information

Dysmorphic Features

Neurological Symptoms

Seizures

Optical and Audiological Symptoms

Musculoskeletal Symptoms