Rothmund-thomson Syndrome malady

Genetics Home Reference: Rothmund-Thomson syndrome is a rare condition that affects many parts of the body, particularly the skin. People with this condition typically develop redness on the cheeks between ages 3 months and 6 months. Over time the rash spreads to the arms and legs, causing patchy changes in skin coloring, areas of skin tissue degeneration (atrophy), and small clusters of enlarged blood vessels just under the skin (telangiectases). These skin problems persist for life, and are collectively known as poikiloderma.¹⁷

MalaCards: Rothmund-thomson Syndrome, also known as poikiloderma atrophicans and cataract, is related to breast cancer and poikiloderma with neutropenia. An important gene associated with Rothmund-thomson Syndrome is USB1 (U6 snRNA biogenesis 1), and among its related pathways are Homologous recombination and Meiotic Recombination. The compounds 8-hydroxyadenine and thymine have been mentioned in the context of this disorder. Affiliated tissues include skin, and related mouse phenotypes are embryogenesis and mortality/aging.

NIH Rare Diseases: Rothmund Thomson syndrome is a genetic condition that affects many parts of the body. It is characterized by distinctive abnormalities of the skin; sparse hair, eyelashes and/or eyebrows; small stature; skeletal and dental abnormalities; and an increased risk of developing osteosarcoma, a cancer of the bone. Rothmund Thomson syndrome is inherited in an autosomal recessive pattern. Mutations in the RECQL4 gene cause about two-thirds of all cases. In the other one-third of cases, the cause is unknown.³⁰

Wikipedia: Rothmund–Thomson syndrome (RTS), also known as poikiloderma atrophicans with cataract or poikiloderma...⁴⁴ more...

OMIM: 268400

GeneReviews summary for rts

Aliases & Descriptions:

rothmund-thomson syndrome 6 7 15 17 8 33 32 43 poikiloderma atrophicans and cataract 30 17 rothmund thomson syndrome 30 16 poikiloderma congenitale 30 17 congenital poikiloderma 6 17

rts 6 17 rothmund-thomson syndrome (disorder) 6 poikiloderma of rothmund-thomson 30 erythrokeratodermia variabilis 43 poikiloderma 43

Diseases related to rothmund-thomson syndrome by text searches and GeneDecks gene sharing:

(show top 50)    (show all 203)

id	Related Disease	Score	Top Affiliating Genes
1	breast cancer	33.6	BLM, HELLS, WRN
2	poikiloderma with neutropenia	31.2	USB1, RECQL4
3	baller-gerold syndrome	30.7	RECQL5, RECQL, RECQL4
4	werner syndrome	29.9	TOP3A, HELLS, BLM, RECQL5, RECQL4, RECQL
5	leukemia	29.4	BLM, SCIN, RECQL4, EP300, WRN, HELLS
6	bloom syndrome	28.6	WRN, TOP3A, HELLS, BLM, RECQL5, RECQL4
7	fanconi anemia, complementation group m	12.8	BLM, TOP3A
8	xeroderma pigmentosum	12.7	RECQL, RECQL4, HELLS
9	vulvar cancer	12.5	WRN, HELLS
10	mayer-rokitansky-kuster-hauser syndrome	12.5	BLM, RECQL4, WRN, HELLS
11	cockayne syndrome	12.4	EP300, HELLS, WRN
12	breast cancer susceptibility	12.4	BLM, HELLS, WRN
13	rapadilino syndrome	12.3	RECQL4, UBR2, WRN
14	ataxia telangiectasia	12.2	WRN, TOP3A, HELLS, BLM
15	erythrokeratodermia variabilis	11.3
16	carcinoma	9.8
17	erythrokeratodermia variabilis et progressiva	9.8
18	erythrokeratodermia variabilis with erythema gyratum repens	9.3
19	osteosarcoma	9.0
20	erythrokeratodermia variabilis 3	8.7
21	gjb3-related erythrokeratodermia variabilis	8.7
22	gjb4-related erythrokeratodermia variabilis	8.7
23	prostatitis	8.6
24	melanoma	8.6
25	thyroiditis	8.3
26	colorectal cancer	8.2
27	gastric cancer	8.2
28	prostate cancer	8.1
29	myeloid leukemia	7.9
30	peritonitis	7.7
31	squamous cell carcinoma	7.6
32	erythrokeratoderma	7.6
33	immunodeficiency	7.6
34	neutropenia	7.6
35	combined immunodeficiency	7.6
36	dyskeratosis congenita	7.6
37	dyskeratosis	7.6
38	acute myeloid leukemia	7.5
39	colon cancer	7.5
40	lung cancer	7.3
41	spastic paraplegia neuropathy poikiloderma	7.3
42	kindler syndrome	7.3
43	keratoderma palmoplantaris transgrediens	7.2
44	skin disease	7.2
45	acute promyelocytic leukemia	7.2
46	adenocarcinoma	7.2
47	thyroid carcinoma	7.2
48	pancreatitis	7.0
49	sarcoma	7.0
50	breast carcinoma	7.0

Clinical features from OMIM: 268400

Approved drugs:

Drug clinical trials:

Genetic tests related to rothmund-thomson syndrome:

id	Genetic test	Affiliating Genes
1	Rothmund-thomson Syndrome clinical/research	RECQL4

MalaCards organs/tissues related to rothmund-thomson syndrome:

²²

MGI Mouse Phenotypes related to rothmund-thomson syndrome:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	embryogenesis phenotype	MP:0005380	6.7	EP300, TOP3A, HELLS, MCM10, CDC45, UBR2
2	mortality/aging	MP:0010768	6.7	WRN, TOP3A, HELLS, MCM10, CDC45, UBR2
3	cellular phenotype	MP:0005384	6.1	RECQL, EP300, WRN, TOP3A, HELLS, MCM10

Articles related to rothmund-thomson syndrome:

(show all 24)

id	Title	Authors	Year	Affiliating Genes
1	Mutations in C16orf57 and normal-length telomeres uni fy a subset of patients with dyskeratosis congenita, poikiloderma with neutrope nia and Rothmund-Thomson syndrome. (20817924)	Walne A.J.... Dokal I.	2010	USB1
2	Rothmund-Thomson syndrome helicase, RECQ4: on the cro ssroad between DNA replication and repair. (20096650)	Liu Y.	2010	RECQL4, HELLS
3	Dual DNA unwinding activities of the Rothmund-Thomson syndrome protein, RECQ4. (19177149)	Xu X.... Liu Y.	2009	RECQL, RECQL4, HELLS
4	p300-mediated acetylation of the Rothmund-Thomson-syndrome gene product RECQL4 regulates its subcellular localization. (19299466)	Dietschy T.... Stagljar I.	2009	EP300, RECQL4
5	Sensitivity of RECQL4-deficient fibroblasts from Rothmund-Thomson syndrome patients to genotoxic agents. (18504617)	Jin W.... Wang L.L.	2008	BLM, WRN, RECQL4
6	Radiographic abnormalities in Rothmund-Thomson syndrome and genotype-phenotype correlation with RECQL4 mutation status. (18647888)	Mehollin-Ray A.R.... Wang L.L.	2008	RECQL4
7	Clinicopathologic features of osteosarcoma in patients with Rothmund-Thomson syndrome. (17264332)	Hicks M.J.... Wang L.L.	2007	RECQL4
8	Biochemical characterization of the RECQ4 protein, mutated in Rothmund-Thomson syndrome. (16214424)	Macris M.A.... Sung P.	2006	RECQL4
9	Rothmund-Thomson syndrome and RECQL4 defect: splitting and lumping. (16271439)	Larizza L.... Roversi G.	2006	RECQL4
10	RECQL4-deficient cells are hypersensitive to oxidative stress/damage: Insights for osteosarcoma prevalence and heterogeneity in Rothmund-Thomson syndrome. (16678792)	Werner S.R.... Hock J.M.	2006	RECQL4
11	Successful umbilical cord blood stem cell transplantation in a patient with Rothmund-Thomson syndrome and combined immunodeficiency. (16630167)	Broom M.A.... Shah M.	2006	RECQL4
12	A patient with Rothmund-Thomson syndrome and all features of RAPADILINO. (15897384)	Kellermayer R.... Kosztolanyi G.	2005	RECQL4
13	Clericuzio type poikiloderma with neutropenia is distinct from Rothmund-Thomson syndrome. (15558713)	Van Hove J.L.... Boogaerts M.	2005	RECQL4
14	Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome. (15960976)	Sangrithi M.N.... Venkitaraman A.R.	2005	RECQL4, CDC45
15	The human Rothmund-Thomson syndrome gene product, RECQL4, localizes to distinct nuclear foci that coincide with proteins involved in the maintenance of genome stability. (16141230)	Petkovic M.... Stagljar I.	2005	RECQL4
16	Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. (12734318)	Wang L.L.... Plon S.E.	2003	RECQL4
17	Preparation of the gene targeted knockout mice for human premature aging diseases, Werner syndrome, and Rothmund-Thomson syndrome caused by the mutation of DNA helicases (11979727)	Ichikawa K.... Furuichi Y.	2002	BLM, WRN, RECQL
18	Rothmund-Thomson syndrome, trisomy 8 mosaicism and RECQ4 gene mutation (12218919)	Durand F.... Modiano P.	2002	RECQL4
19	An unusual mutation in RECQ4 gene leading to Rothmund-Thomson syndrome. (12379465)	Balraj P.... Volpi L.	2002	RECQL4
20	Intron-size constraint as a mutational mechanism in Rothmund-Thomson syndrome. (12016592)	Wang L.L.... Plon S.E.	2002	RECQL4
21	Rothmund-Thomson syndrome due to RECQ4 helicase mutations: report and clinical and molecular comparisons with Bloom syndrome and Werner syndrome. (10678659)	Lindor N.M.... Jalal S.	2000	RECQL4
22	Rothmund-Thomson syndrome responsible gene, RECQL4: genomic structure and products. (10552928)	Kitao S.... Shimamoto A.	1999	RECQL4
23	Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. (10319867)	Kitao S.... Furuichi Y.	1999	WRN, RECQL4, RECQL5
24	Rothmund-Thomson Syndrome (20301415)	Wang L.L.... Plon S.E.	1993	RECQL4

Genes related to rothmund-thomson syndrome according to GeneCards:

(show all 14)

id	Symbol	Description	Score	GeneCards Section Context
1	USB1	U6 snRNA biogenesis 1	11.1	Summaries, Disorders, Publications
2	RECQL4	RecQ protein-like 4	11.1	Publications
3	RECQL	RecQ protein-like (DNA helicase Q1-like)	11.1	Disorders, Publications
4	RECQL5	RecQ protein-like 5	11.1	Publications, Disorders
5	BLM	Bloom syndrome, RecQ helicase-like	11.1	Publications
6	WRN	Werner syndrome, RecQ helicase-like	11.1	Publications
7	HELLS	helicase, lymphoid-specific	11.1	Publications
8	GINS4	GINS complex subunit 4 (Sld5 homolog)	11.0	Disorders
9	CDC45	cell division cycle 45 homolog (S. cerevisiae)	11.0	Publications
10	TOP3A	topoisomerase (DNA) III alpha	11.0
11	MCM10	minichromosome maintenance complex component 10	11.0	Disorders
12	UBR2	ubiquitin protein ligase E3 component n-recognin 2	11.0
13	SCIN	scinderin	11.0
14	EP300	E1A binding protein p300	11.0	Publications

Pathways related to rothmund-thomson syndrome according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Homologous recombination20	9.7	BLM, TOP3A
2	Meiotic Recombination38	9.6	BLM, TOP3A
3	Cell Cycle / Checkpoint Control3	9.2	CDC45, BLM, RECQL5, RECQL4
4	DNA Damage3	9.1	RECQL, RECQL4, RECQL5, BLM, WRN
5	Cell Cycle, Mitotic38	8.9	CDC45, MCM10, GINS4

Compounds related to rothmund-thomson syndrome according to GeneDecks:

id	Compound	Score	Top Affiliating Genes
1	8-hydroxyadenine32	9.8	WRN, HELLS
2	thymine32 18	10.6	HELLS, EP300
3	8-oxoguanine32	9.4	HELLS, WRN, EP300
4	camptothecin32 42 9 9	12.2	BLM, WRN, EP300
5	methylmethanesulfonate32	9.2	WRN, TOP3A, HELLS, BLM
6	hydroxyurea32 9 9	10.9	RECQL4, BLM, HELLS, TOP3A, WRN
7	atp32	8.4	EP300, WRN, HELLS, BLM, RECQL

Cellular components related to rothmund-thomson syndrome according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	nucleoplasm	GO:005654	8.0	RECQL5, CDC45, MCM10, GINS4, WRN, EP300
2	nucleolus	GO:005730	7.3	EP300, WRN, MCM10, UBR2, BLM, RECQL5
3	nucleus	GO:005634	5.8	RECQL, EP300, WRN, TOP3A, HELLS, MCM10

Biological processes related to rothmund-thomson syndrome according to GeneDecks:

(show all 8)

id	Name	GO ID	Score	Top Affiliating Genes
1	DNA strand renaturation	GO:000733	10.0	RECQL, RECQL4
2	replication fork processing	GO:031297	9.9	BLM, WRN
3	DNA strand elongation involved in DNA replication	GO:006271	9.7	CDC45, GINS4
4	DNA metabolic process	GO:006259	9.6	RECQL5, WRN
5	DNA duplex unwinding	GO:032508	9.5	WRN, RECQL5, RECQL4, RECQL
6	DNA repair	GO:006281	9.3	BLM, RECQL5, RECQL4, RECQL
7	DNA recombination	GO:006310	9.2	RECQL, RECQL4, RECQL5, BLM, WRN
8	DNA replication	GO:006260	8.8	WRN, MCM10, CDC45, RECQL4, RECQL

Molecular functions related to rothmund-thomson syndrome according to GeneDecks:

(show all 8)

id	Name	GO ID	Score	Top Affiliating Genes
1	four-way junction helicase activity	GO:009378	9.9	WRN, BLM
2	G-quadruplex DNA binding	GO:051880	9.8	BLM, WRN
3	bubble DNA binding	GO:000405	9.7	RECQL4, BLM, WRN
4	DNA helicase activity	GO:003678	9.7	WRN, RECQL5, RECQL
5	ATP-dependent DNA helicase activity	GO:004003	9.7	RECQL, BLM, WRN
6	ATP-dependent 3-5 DNA helicase activity	GO:043140	9.5	RECQL, RECQL4, BLM, WRN
7	helicase activity	GO:004386	9.2	BLM, HELLS, WRN
8	ATP binding	GO:005524	8.2	TOP3A, HELLS, BLM, RECQL5, RECQL4, RECQL