GM20136
Fibroblast from Skin, Unspecified
Description:
MUCOLIPIDOSIS IIIA
N-ACETYLGLUCOSAMINE-1-PHOSPHOTRANSFERASE, ALPHA/BETA SUBUNITS; GNPTAB
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases
Lysosomal Storage Diseases |
| Class |
Disorders of Carbohydrate Metabolism |
|
Biopsy Source
|
Unspecified
|
|
Cell Type
|
Fibroblast
|
|
Tissue Type
|
Skin
|
|
Transformant
|
Untransformed
|
|
Sample Source
|
Fibroblast from Skin, Unspecified
|
|
Race
|
White
|
|
Ethnicity
|
SWISS-EMMENTAL
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Molecular characterization before cell line submission to CCR
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin confirmed by LINE assay |
| |
| Gene |
GNPTAB |
| Chromosomal Location |
12q23.3 |
| Allelic Variant 1 |
607840.0001; MUCOLIPIDOSIS IIIA, ATYPICAL |
| Identified Mutation |
G>A,EX7; In a 47-year-old female who presented with dilated cardiomyopathy and mild neuropathy and was found to have mucolipidosis III (252600), Steet et al. (2005) identified a homozygous G-A transition in the last nucleotide of exon 7 of the GNPTA gene, resulting in skipping of exon 7 and the production of a minimal amount of functional enzyme. The patient exhibited none of the connective tissue anomalies characteristic of mucolipidosis III, and the authors stated that this was the first example of the disease presenting in an adult patient. |
| |
| Gene |
GNPTAB |
| Chromosomal Location |
12q23.3 |
| Allelic Variant 2 |
607840.0001; MUCOLIPIDOSIS IIIA, ATYPICAL |
| Identified Mutation |
G>A,EX7; In a 47-year-old female who presented with dilated cardiomyopathy and mild neuropathy and was found to have mucolipidosis III (252600), Steet et al. (2005) identified a homozygous G-A transition in the last nucleotide of exon 7 of the GNPTA gene, resulting in skipping of exon 7 and the production of a minimal amount of functional enzyme. The patient exhibited none of the connective tissue anomalies characteristic of mucolipidosis III, and the authors stated that this was the first example of the disease presenting in an adult patient. |
| Remarks |
Clinically affected; healthy childhood and adolescence; presented at age 47 with non-familial subacute tetraspastic syndrome in combination with hyposensibility and paresthesias of the distal upper and lower extremities; sensory neuropathy was diagnosed by orthodromic neurography; several months after the sensory neuropathy was diagnosed a discrete lower extremity motor neuropathy was detectable; spinal cord and cerebral MRI showed an old thromboembolic cerebral infarction in the left frontal lobe that was not apparent clinically; biventricular cardiomyopathy; heart failure worsened in the several years after diagnosis of cardiomyopathy and an endomyocardial biopsy demonstrated hypertrophied cardiomyocytes with birefringent inclusion bodies and electron microscopy revealed prominent lysosomes containing rolled lipid bilayers; at autopsy, neural tissue found to contain inclusions similar to those observed in myocardial tissue but the number of inclusion bodies per cell was smaller; joint mobility and skin normal; unremarkable right hand films; clinical and autopsy findings indicate a mild form of ML III with an atypical clinical presentation, including lack of connective tissue and skeletal abnormalities; lysosomal enzymes elevated in subject's serum include: alpha-iduronidase, beta-glucuronidase, alpha-galactosidase, beta-galactosidase, beta-hexosaminidase A+B, alpha-fucosidase, arylsulfatase A, acid phosphatase; levels of beta-glucuronidase, beta-galactosidase, and alpha-fucosidase in skin fibroblasts were not decreased to the same extent as usually observed in ML III patients; beta-hexosaminidase A+B were decreased in skin fibroblasts; activity of GlcNAc-1-phosphotransferase enzyme in fibroblast extracts was 3.2 +/- 2.7% of control samples; donor subject is homozygous for a G>A transition in the last nucleotide in exon 7 of the GNPTAB gene resulting in aberrant splicing and skipping of exon 7 [G>A, Ex7]. |
| Steet RA, Hullin R, Kudo M, Martinelli M, Bosshard NU, Schaffner T, Kornfeld S, Steinmann B, A splicing mutation in the alpha/beta GlcNAc-1-phosphotransferase gene results in an adult onset form of mucolipidosis III associated with sensory neuropathy and cardiomyopathy. Am J Med Genet A132(4):369-75 2005 |
| PubMed ID: 15633164 |
| Split Ratio |
1:2 |
| Temperature |
37 C |
| Percent CO2 |
8% |
| Medium |
Dulbecco Modified Eagles Medium (high glucose) with 2mM L-glutamine or equivalent |
| Serum |
10% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
Sodium Pyruvate 100mM |
|