Boni, Lorenzo Comas Illas, Juan Valentín Mendoza Soto, Alberto
Identification of de novo mutations and rare variants in hypoplastic left heart syndrome. [artículo] - Clinical Genetics, 2012 - 81(6):542-54
Formato Vancouver:
Iascone M, Ciccone R, Galletti L, Marchetti D, Seddio F, Lincesso AR, et al. Identification of de novo mutations and rare variants in hypoplastic left heart syndrome. Clin Genet. 2012 Jun;81(6):542-54.
PMID: 21457232
Contiene 29 referencias
Hypoplastic left heart syndrome (HLHS) is one of the most severe congenital heart malformations, characterized by underdevelopment of the structures in the left heart–aorta complex. The majority of cases are sporadic. Although multiple genetic loci have been tentatively implicated in HLHS, no gene or pathway seems to be specifically associated with the
disease. To elucidate the genetic basis of HLHS, we analyzed 53 well-characterized patients with isolated HLHS using an integrated genomic approach that combined DNA sequencing of five candidate genes (NKX2-5, NOTCH1, HAND1, FOXC2 and FOXL1) and genome-wide screening by high-resolution array comparative genomic hybridization. In 30 patients, we identified two novel de novo mutations in NOTCH1, 23 rare patients inherited gene variants in NOTCH1, FOXC2 and FOXL1, and
33 rare patients mostly inherited copy-number variants. Some of the identified variations coexisted in the same patient. The biological significance of such rare variations is unknown, but our findings strengthen the role of NOTCH pathway in cardiac valve development, indicating that HLHS is, at least in part, a ‘valve’ disease. This is the first report of de novo mutations associated with isolated HLHS. Moreover, the coexistence of multiple rare variants suggests in some cases a cumulative effect, as
shown for other complex disease.
Identification of de novo mutations and rare variants in hypoplastic left heart syndrome. [artículo] - Clinical Genetics, 2012 - 81(6):542-54
Formato Vancouver:
Iascone M, Ciccone R, Galletti L, Marchetti D, Seddio F, Lincesso AR, et al. Identification of de novo mutations and rare variants in hypoplastic left heart syndrome. Clin Genet. 2012 Jun;81(6):542-54.
PMID: 21457232
Contiene 29 referencias
Hypoplastic left heart syndrome (HLHS) is one of the most severe congenital heart malformations, characterized by underdevelopment of the structures in the left heart–aorta complex. The majority of cases are sporadic. Although multiple genetic loci have been tentatively implicated in HLHS, no gene or pathway seems to be specifically associated with the
disease. To elucidate the genetic basis of HLHS, we analyzed 53 well-characterized patients with isolated HLHS using an integrated genomic approach that combined DNA sequencing of five candidate genes (NKX2-5, NOTCH1, HAND1, FOXC2 and FOXL1) and genome-wide screening by high-resolution array comparative genomic hybridization. In 30 patients, we identified two novel de novo mutations in NOTCH1, 23 rare patients inherited gene variants in NOTCH1, FOXC2 and FOXL1, and
33 rare patients mostly inherited copy-number variants. Some of the identified variations coexisted in the same patient. The biological significance of such rare variations is unknown, but our findings strengthen the role of NOTCH pathway in cardiac valve development, indicating that HLHS is, at least in part, a ‘valve’ disease. This is the first report of de novo mutations associated with isolated HLHS. Moreover, the coexistence of multiple rare variants suggests in some cases a cumulative effect, as
shown for other complex disease.
