Description:
WERNER SYNDROME; WRN REPLICATION FOCUS-FORMING ACTIVITY 1, INCLUDED; FFA1, INCLUDED
LAMIN A/C; LMNA
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Repository
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NIA Aging Cell Culture Repository
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| Subcollection |
Heritable Diseases |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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White
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Ethnicity
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PORTUGESE
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Relation to Proband
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proband
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Confirmation
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Molecular characterization before cell line submission to CCR
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ISCN
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46,XX
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin confirmed by LINE assay |
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| Gene |
LMNA |
| Chromosomal Location |
1q21.2 |
| Allelic Variant 1 |
150330.0027; WERNER SYNDROME, ATYPICAL |
| Identified Mutation |
ARG133LEU; In 2 unrelated persons in whom a diagnosis of Werner syndrome (277700) had been made but no mutation found in the Werner syndrome gene (RECQL2; 604611), Chen et al. (2003) found heterozygosity for the R1333L mutation in the LMNA gene. One was a white Portuguese female who presented at the age of 9 years with short stature. She showed scleroderma-like skin changes and graying/thinning of hair. Type 2 diabetes developed at the age of 23 years. Hypogonadism, osteoporosis, and voice changes were also present. The other patient was an African American female in whom the diagnosis of Werner syndrome was made at the age of 18 years. Scleroderma-like skin, short stature, graying/thinning of hair, and type 2 diabetes at the age of 18 years were features. The deceased father, paternal aunt, and paternal grandmother of this patient were also diagnosed with severe insulin-resistant diabetes mellitus, suggesting that the R133L mutation might have been paternally inherited. |
| Remarks |
Atypical; clinically affected; Portugese; atypical; fractured patella at age 10; decreased bone density; growth failure; poor secondary sexual development; chronic diarrhea; tired; graying hair; thin skin; loss of subcutaneous fat, particularly in legs; anorexia; high aminotransferase levels; some hepatomegaly; heart murmur; height = 151 cm at age 13 yr. This donor is heterozygous for a G-to-T substitution at nucleotide 813 (813G>T) in exon 2 of the LMNA gene, resulting in a missense mutation in codon 133 [ARG133LEU (R133L)]. |
| Heyn H, Moran S, Esteller M, Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome. Epigenetics8(1):28-33 2013 |
| PubMed ID: 23257959 |
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| Chen L, Lee L, Kudlow BA, Dos Santos HG, Sletvold O, Shafeghati Y, Botha EG, Garg A, Hanson NB, Martin GM, Mian IS, Kennedy BK, Oshima J, LMNA mutations in atypical Werner's syndrome. Lancet362(9382):440-5 2003 |
| PubMed ID: 12927431 |
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