GM27686

GM27686 LCL from B-Lymphocyte

Description:

GLUT1 DEFICIENCY SYNDROME 1; GLUT1DS1
SOLUTE CARRIER FAMILY 2 (FACILITATED GLUCOSE TRANSPORTER), MEMBER 1; SLC2A1

Affected:

Yes

Sex:

Female

Age:

15 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

Subject Type

parent/child concordant pair

Ethnicity

Not Hispanic/Latino

Ethnicity

Jewish Ashkenazi

Country of Origin

ISRAEL

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. Patient 1 in the publication (PMID: 23340081). See the 'Phenotypic Data" tab. Heterozygous mutation in the SLC2A1 gene: R218H and R458W in the same allele. Clinically affected mother is GM27687 (LCL).

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

Gene

SLC2A1

Chromosomal Location

1p34.2

Allelic Variant 1

; GLUT1 DEFICIENCY SYNDROME 1; GLUT1DS1

Identified Mutation

c.653G>A (p.Arg218His); Conflicting interpretations of pathogenicity

Gene

SLC2A1

Chromosomal Location

1p34.2

Allelic Variant 1

138140.0021; GLUT1 DEFICIENCY SYNDROME 1; GLUT1DS1

Identified Mutation

c.1372C>T (p.Arg458Trp); In a 30-year-old man with idiopathic generalized epilepsy (EIG12; 614847), Arsov et al. (2012) identified a heterozygous c.1372C-T transition in exon 10 of the SLC2A1 gene, resulting in an arg458-to-trp (R458W) substitution at a highly conserved residue. In vitro functional expression studies in Xenopus oocytes showed that the R458W substitution caused a marked reduced in glucose transport. The patient had onset of childhood absence epilepsy at age 6 and developed paroyxsmal exertional dyskinesia in his teens. He also had arm dystonia. The patient's father, who also carried the mutation, had onset of childhood absence seizures at age 7, developed PED as an adult, and had disabling leg dyskinesia when walking. The father's unaffected 66-year-old sister also carried the mutation, indicating incomplete penetrance. The proband was identified from a cohort of 504 probands with IGE who underwent direct sequencing of the SLC2A1 gene. The mutation was not found in 470 controls and had not previously been reported in databases of normal human genetic variation.

Phenotypic Data

Demographic Data

Relation to Proband

proband

Age at Sampling

15 YR

Sex

Female

Age of Onset(If not a control)

2 YR

Age at Diagnosis(If not a control)

4 YR

Hispanic or Latino/Not Hispanic or Latino

Not Hispanic/Latino

Racial Category

White

Country

ISRAEL

Data Elements

Clinical Element Type: General NIGMS Catalog Remarks

(Baseline)

Mutation Information

Gene, variant, consequence, and exon number:

SLC2A1, R218H, MISSENSE, EXON 5

Zygosity:

Heterozygous

Other variants:

SLC2A1, R458W, MISSENSE, EXON 10

Age of Symptom Onset and Age at Diagnosis

Age of Symptom Onset:

1.5 TO 2 YEARS

Age at Diagnosis:

4 YEARS AND 10 MONTHS

In Utero History Information

Birth History Information

Dysmorphic Features

Neurological Symptoms

Seizures
Sleep abnormalities

Additional Information:

HEADACHE

Optical and Audiological Symptoms

Musculoskeletal Symptoms

Developmental Milestones

Gastrointestinal Symptoms

Genitourinary Symptoms

Respiratory and Cardiovascular Symptoms

Cognitive and Behavioral Symptoms

Attention deficit hyperactivity disorder

Additional Information:

MONOTONICALLY SLOW TROUBLE AT CUTTING AND DRAWING IN THE LINES BEFORE DIET SLOW COPYING FROM THE BOARD

Additional Information

Testing Performed

Neurological Testing:

EEG: FAST PSW PROMINENT IN SLEEP

Treatments and Assistive Devices

Occupational therapy
Physical therapy
Speech therapy

Additional Testing:

PSYCHOLOGICAL THERAPY

Medications

MODIFIED ATKINS KETOGENIC DIET MCT OIL CALCIUM WITH MAGNESIUM RISPERDAL MULTI-VITAMINS

Family History

3 GENERATIONS OF 10 CASES IN TOTAL (SEE PMID: 23340081) FOR THE PEDIGREE TREE GRANDFATHER, MOTHER, 2 SIBLINGS, 5 UNCLES/AUNTS

Remarks

Publications

Tzadok M, Nissenkorn A, Porper K, Matot I, Marcu S, Anikster Y, Menascu S, Bercovich D, Ben Zeev B, The many faces of Glut1 deficiency syndrome Journal of child neurology29:349-59 2013

PubMed ID: 23340081