RESUMEN
We performed a genetic analysis of 331 non-syndromic cleft lip with or without cleft palate (CL +/- P) proband families ascertained in Madras, India. Predictions of the multifactorial threshold (MF/T) model are tested; goodness-of-fit tests of the MF/T model and complex segregation analysis are also utilized to clarify the genetic etiology of CL +/- P in this study population. There was little evidence for the MF/T model. The most reasonable conclusion from mixed model analysis is that of a major locus with reduced transmission probability. This is not altogether surprising if manifestation of CL +/- P also depends on in utero exposure to harmful environmental agents during the critical period of facial development, as suggested by Melnick et al. [1980] and demonstrated in an animal model of CL +/- P [Melnick et al., 1981]. Further the results in the Madras population are quite similar to those in other populations of Europe and Asia.
Asunto(s)
Labio Leporino/genética , Fisura del Paladar/genética , Labio Leporino/epidemiología , Fisura del Paladar/epidemiología , Femenino , Humanos , India/epidemiología , Recién Nacido , Masculino , Modelos Genéticos , Factores de Riesgo , Razón de MasculinidadRESUMEN
Monosomy of the entire short arm of chromosome 18 as a result of an 18;acrocentric whole arm translocation has been reported in over 20 patients, 3 of which were familial. The centromeric origin in de novo cases has not been characterized. We report molecular cytogenetic studies of two prenatally-detected de novo cases. Amniocenteses were performed because of sonographic findings of fetal holoprosencephaly. Cytogenetic studies and dual color fluorescence in situ hybridization using Oncor alpha-satellite probes for D18Z1 and D13Z1/D21Z1 showed monosomy 18p with presence of a dicentric 18;21 chromosome in both cases [45,XY,dic(18;21)(p11.1;p11.1)]. In one case, a second cell line was found, which contained 46 chromosomes with a del(18)(p11.1) and an apparently telocentric 21 not present in either parent [46,XY,del(18)(p11.1),del(21)(p11.1)]. The del(18)(p11.1) contained only the 18 alphoid sequence and the telocentric 21 contained only the 21 alphoid sequence. No centromeric break was detected. We propose that the second cell line arose from dissociation of the dic(18;21) with no centromeric DNA break. In addition to our case, there have been three previous reports of dissociation of dicentric 18;acrocentric chromosomes indicating that the translocation site can be unstable and dissociate.
Asunto(s)
Cromosomas Humanos Par 18 , Cromosomas Humanos Par 21 , Holoprosencefalia/genética , Monosomía , Translocación Genética , Adulto , Amniocentesis , Centrómero , Bandeo Cromosómico , Mapeo Cromosómico , ADN Satélite , Femenino , Marcadores Genéticos , Holoprosencefalia/diagnóstico , Holoprosencefalia/embriología , Humanos , Recién Nacido , Cariotipificación , Masculino , Embarazo , Ultrasonografía PrenatalRESUMEN
A case of acute monocytic leukemia (FAB-M5b) expressing natural killer cell-associated antigens containing a t(8;14)(p11;q11.1) is presented. We interpret this translocation to represent a variant of the t(8;16) previously reported in FAB-M5b. These findings support the contention that the 8p11 breakpoint site is the critical junction in the oncogenesis of acute monoblastic leukemia with differentiation.