AG05013

AG05013 Fibroblast from Skin, Arm

Description:

ROTHMUND-THOMSON SYNDROME; RTS
RECQ PROTEIN-LIKE 4; RECQL4
NIA AGING CELL REPOSITORY DNA PANEL - AGING SYNDROMES

Affected:

Yes

Sex:

Male

Age:

10 YR (At Sampling)

Overview

Repository

NIA Aging Cell Culture Repository

Subcollection

Heritable Diseases

Biopsy Source

Arm

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Arm

Race

White

Relation to Proband

proband

Confirmation

Clinical summary/Case history

ISCN

46,XY[19]

Species

Homo sapiens

Common Name

Human

Remarks

The donor had features of short stature, sparse hair, characteristic facies, poikiloderma, absent right thumb and hyperplastic left thumb. The family history is negative. The biopsy was taken ante-mortem in 1973 from skin on the mesial aspect of the arm. The cell morphology is fibroblastlike. The karyotype is 46,XY; normal diploid male with 14% of cells examined showing chromosome breakage. The donor subject is a compound heterozygote for two frameshift mutations in the RECQL4 gene: one allele carries a 2 bp deletion at nucleotide position 2492 (2-BP DEL, NT2492) and the second allele has a G-to-T transversion at the junction of intron 12 and exon 13 that destroys the splicing acceptor sequence (IVS12AS, G>T, -1). The legacy karyotype description shown in this Remark may not be representative of the current available product.

Characterizations

PDL at Freeze

7.38

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Chromosome Analysis

Gene

RECQL4

Chromosomal Location

8q24.3

Allelic Variant 1

603780.0003; ROTHMUND-THOMSON SYNDROME

Identified Mutation

2-BP DEL, NT2492; In cells of an Rothmund-Thomson syndrome (RTS; 268400) patient of European descent deposited in the cell bank of the National Institute of Aging (AG05013), Kitao et al. [Genomics 54: 443-452 (1998)] found compound heterozygosity for 2 mutations of the RECQL4 gene: a 2-bp deletion (designated mut-3) and a G-to-T transversion at the junction of intron 12 and exon 13 that destroyed the splicing acceptor sequence (mut-4). Both mutations were associated with a translational frameshift. Exon 13 was deleted in the case of the mut-4 allele.

Gene

RECQL4

Chromosomal Location

8q24.3

Allelic Variant 2

603780.0004; ROTHMUND-THOMSON SYNDROME

Identified Mutation

IVS12AS, G>T, -1; In cells of an Rothmund-Thomson syndrome (RTS; 268400) patient of European descent deposited in the cell bank of the National Institute of Aging (AG05013), Kitao et al. [Genomics 54: 443-452 (1998)] found compound heterozygosity for 2 mutations of the RECQL4 gene: a 2-bp deletion (designated mut-3) and a G-to-T transversion at the junction of intron 12 and exon 13 that destroyed the splicing acceptor sequence (mut-4). Both mutations were associated with a translational frameshift. Exon 13 was deleted in the case of the mut-4 allele. See also Kitao et al. [Nature Genet. 22: 82-84 (1999)].

Phenotypic Data

Remarks

Publications

Yokoyama H, Moreno-Andres D, Astrinidis SA, Hao Y, Weberruss M, Schellhaus AK, Lue H, Haramoto Y, Gruss OJ, Antonin W, Chromosome alignment maintenance requires the MAP RECQL4, mutated in the Rothmund-Thomson syndrome Life science alliance2: 2018

PubMed ID: 30718377

Schurman SH, Hedayati M, Wang Z, Singh DK, Speina E, Zhang Y, Becker K, Macris M, Sung P, Wilson DM, Croteau DL, Bohr VA, Direct and indirect roles of RECQL4 in modulating base excision repair capacity Human molecular genetics18:3470-83 2009

PubMed ID: 19567405

Fan W, Luo J, RecQ4 facilitates UV-induced DNA damage repair through interaction with nucleotide excision repair factor XPA The Journal of biological chemistry18:3470-83 2008

PubMed ID: 18693251

Yin J, Kwon YT, Varshavsky A, Wang W, RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway. Hum Mol Genet13(20):2421-30 2004

PubMed ID: 15317757

Kitao S, Shimamoto A, Goto M, Miller RW, Smithson WA, Lindor NM, Furuichi Y, Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. Nat Genet22:82-4 1999

PubMed ID: 10319867

Kitao S, Ohsugi I, Ichikawa K, Goto M, Furuichi Y, Shimamoto A, Cloning of two new human helicase genes of the RecQ family: biological significance of multiple species in higher eukaryotes. Genomics54:443-52 1998

PubMed ID: 9878247