000			02449na a2200253 4500
003			H12O
005			20180417112254.0
008			130622s2012 xxx||||| |||| 00| 0 eng d
040			_cH120
041			_aeng
100			_aBoni, Lorenzo _92095 _eCirugía Cardiaca
100			_aComas Illas, Juan Valentín _91849 _eCirugía Cardíaca Pediátrica
100			_aMendoza Soto, Alberto _9849 _ePediatría
245	0	0	_aIdentification of de novo mutations and rare variants in hypoplastic left heart syndrome. _h[artículo]
260			_bClinical Genetics, _c2012
300			_a81(6):542-54
500			_aFormato 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.
501			_aPMID: 21457232
504			_aContiene 29 referencias
520			_aHypoplastic 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.
710			_9446 _aServicio de Pediatría-Neonatología
856			_uhttp://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/3/pc3273.pdf _ySolicitar documento
942			_n0 _2ddc _cART
999			_c3273 _d3273