EMAIL THIS PAGE TO A FRIEND

Genes & development

Hoyeraal-Hreidarsson syndrome caused by a germline mutation in the TEL patch of the telomere protein TPP1.


PMID 25233904

Abstract

Germline mutations in telomere biology genes cause dyskeratosis congenita (DC), an inherited bone marrow failure and cancer predisposition syndrome. DC is a clinically heterogeneous disorder diagnosed by the triad of dysplastic nails, abnormal skin pigmentation, and oral leukoplakia; Hoyeraal-Hreidarsson syndrome (HH), a clinically severe variant of DC, also includes cerebellar hypoplasia, immunodeficiency, and intrauterine growth retardation. Approximately 70% of DC cases are associated with a germline mutation in one of nine genes, the products of which are all involved in telomere biology. Using exome sequencing, we identified mutations in Adrenocortical Dysplasia Homolog (ACD) (encoding TPP1), a component of the telomeric shelterin complex, in one family affected by HH. The proband inherited a deletion from his father and a missense mutation from his mother, resulting in extremely short telomeres and a severe clinical phenotype. Characterization of the mutations revealed that the single-amino-acid deletion affecting the TEL patch surface of the TPP1 protein significantly compromises both telomerase recruitment and processivity, while the missense mutation in the TIN2-binding region of TPP1 is not as clearly deleterious to TPP1 function. Our results emphasize the critical roles of the TEL patch in proper stem cell function and demonstrate that TPP1 is the second shelterin component (in addition to TIN2) to be implicated in DC.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB1407914
Anti-ACD antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB2100024
Anti-ACD antibody produced in rabbit, affinity isolated antibody
SAB2106190
Anti-ACD antibody produced in rabbit, affinity isolated antibody
HPA057660
Anti-ACD antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1411281
Anti-ACD antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
AV53621
Anti-COIL antibody produced in rabbit, affinity isolated antibody
SAB1411471
Anti-COIL antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB1406522
Anti-TERF2 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB1407307
Anti-TINF2 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB2102430
Anti-TINF2 antibody produced in rabbit, affinity isolated antibody
SAB4501131
Anti-TINF2 antibody produced in rabbit, affinity isolated antibody
WH0065057M2
Monoclonal Anti-ACD antibody produced in mouse, clone 1D8-1B6, purified immunoglobulin, buffered aqueous solution
SAB1405257
Monoclonal Anti-ACD antibody produced in mouse, clone 1C11-1A7, purified immunoglobulin, buffered aqueous solution
SAB4100523
Monoclonal Anti-ACD antibody produced in mouse, clone ACD-A471, culture supernatant
SAB4200108 Monoclonal Anti-TIN2 antibody produced in mouse, ~1.0 mg/mL, clone TIN30, purified immunoglobulin
SAB4200157
Monoclonal Anti-TIN2 antibody produced in mouse, clone MT-28, ~1 mg/mL, purified immunoglobulin
PLA0290
Rabbit anti-Coilin Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.