ABSTRACT
Se reporta el estudio de tres pacientes con un alto grado de consanguinidad. Dos hermanos (hermano y hermana) y un primo hermano de 07, 12 y 03 años respectivamente, con un cuadro clínico de hipoplasia cerebelar severa caracterizada por la presencia de una anomalía en la conformación de las estructuras supratentorial e infratentorial. Presentaron un vermis rudimentario y un tronco cerebral de pequeño tamaño, encontrándose incrementada la cisterna prepontina y una inserción alta del tentorio. Además, presentaron disgenesia del cuerpo calloso, no apreci ndose otras alteraciones a nivel de las estructuras supratentoriales ni asimetría en las circunvoluciones cerebrales. Los pacientes presentaron incoordinación en los movimientos de los ojos y de la cabeza, estrabismo, ptosis bilateral y oftalmoplejia leve; así mismo, ligera macrocefalia, orejas prominentes, escoliosis, presencia de lesiones hiperpigmentadas en la piel y otras manchas hipopigmentadas, hipotonía troncal y axial, nistagmus, bajo peso al nacimiento (2,7 a 2,9 Kg), problemas para la deglución de alimentos sólidos, retardo en el crecimiento y bajo coeficiente intelectual con un vocabulario limitado compuesto por palabras de dos sílabas.
A case of high degree-consanguinity in three patients of 07, 12 and 03 years old (brother, sister and first cousin, respectively) is reported. These patients have cerebellar hypoplasia with anomalous supratentorial and infratentorial structures, rudimentary vermis and small brain trunk, prepontine cysterna shows increased size and high insertion of tentorius is present. Besides, all of the three patients showed callosum corpus dysgenesia, with no other anomalies in supratentorial structures or asymmetric brain sulcus. Patients presented poor eye coordination and head movements, strabismus, bilateral ptosis and mild ophthalmoplegic features. Also, they showed mild macrocephaly, prominent ears, troncal, and axial hipotony, nystagmus, low birth-weight (2,7 - 2,9 Kg), troubles on solid foods deglution, low growth rate and low IQ with limited vocabulary of two syllable words.
Subject(s)
Female , Child, Preschool , Child , Consanguinity , Cerebellar Diseases , Nervous System Diseases , HeredityABSTRACT
Background: In the search of the major genes responsible for the genetic etiology of Nonsyndromic Cleft Lip and Palate (NSCLP), an association study between this malformation and four molecular markers, F13A1 and EDN1 (6p), D17S579 (17q) and BCL3 (19q), was done. Aim: To determine, in a Chilean population, the presence of NSCLP susceptibility regions, as proposed for Caucasian populations in the 6p, 17q and 19q chromosomal regions. Material and Methods: A sample of unrelated NSCLP patients, that belonged to Simplex (Sx) and Multiplex (Mx) families, was analyzed. Blood donors were used as a control group (Co). The DNA of the four markers was amplified by means of PCR, their products analyzed by PAGE denaturants and visualized by silver staining. Statistical analysis was performed using c2 log ratio. Results: Allele frequency distribution of D17S579 was significantly different in all patients with NSCLP and their subgroups, when compared to control subjects. Significant differences in EDN1 frecuency were observed between the total groups of NSCLP patients and those pertaining to the Mx subgroup, when compared to controls. Differences in F13A1 distribution were only observed between NSCLP-Mx patients and controls. There was a slight difference in BCL3 distribution, between the total sample of NSCLP patients and controls. Conclusions: Our results support the hypothesis of the existence of cleft susceptibility regions in 6p and 17q. The small significance of BCL3, suggests that ethnicity can influence the interactions between involved genes
Subject(s)
Humans , Male , Female , Phenotype , Cleft Lip , Cleft Palate , Microsatellite Repeats/genetics , Alleles , Gene FrequencyABSTRACT
Background: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common craniofacial defect. Association studies have suggested that a cleftinglocus is located on chromosome 4q at or near two microsatellite markers D4S175 and D4S192. Aim: To test the hypothesis on the possible presence of a clefting locus on chromosome 4q. Material and methods: We carried out an association study on a sample of unrelated NSCLP patients, of their unaffected relatives and in controls. Both probands and relatives were further analyzed depending if they originated from simplex or multiplex families. DNA was analyzed with two PCR markers close to the putative NSCLP locus, dinucleotide repeats D4S175 and D4S192. PCR products were resolved by PAGE and visualized by silver staining. Statistical analysis was performed by means of c2 log ratio. Results: Significant differences between NSCLP and controls were observed when comparing the allele frequency distribution of D4S192 both in the total sample as well as in NSCLP-multiplex and simplex cases. No significant differences for D4S175 were observed in any of the comparisons. Unaffected relatives showed significant differences with controls both for D4S175 and D4S192. Conclusions: Our results support the hypothesis that a NSCLP locus maps on chromosome 4q close to the microsatellite marker D4S192. No differences were observed between NSCLP multiplex and simplex cases versus controls, implying that they do not represent different etiologic entities. The results of the present and previous studies in the same group of patients support the hypothesis that several major interacting genes participate in the etiology of NSCLP
Subject(s)
Humans , Male , Female , Adult , Cleft Lip/genetics , Cleft Palate/genetics , Microsatellite Repeats/genetics , Phenotype , Case-Control Studies , Gene Frequency/genetics , Gene Amplification/methodsABSTRACT
Background: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common craniofacial developmental defect. Association studies have suggested that a clefting locus is located on chromosome 6p at or near two possible loci, Factor 13A (FI3A) in the region 6p 25-24 and HLA at 6p 21.3. Aim. To test the hypothesis on the possible presence of a major gene on chromosome 6p associated with NSCLP. Patients and methods: We carried out an association study on a sample of unrelated NSCLP patients from multiplex (Mx) and simplex (Sx) families, of their unaffected relatives and in control individuals. DNA was analyzed with three PCR markers close to the putative NSCLP locus, dinucleotide repeats at loci D6S89, D6S109 and D6S105. PCR products were resolved by PAGE and visualized by silver staining. Statistical analysis was performed by means of c2 log ratio. Results: Significant differences were observed when comparing the allele frequency distribution of D6S89 in patients with NSCLP and controls and in patients with NSCLP-Mx and controls. No significant differences were observed for patients with NSCLP-Sx. D6S109 and D6S105 showed no significant differences in any of the comparisons. Conclusions: Our results support the hypothesis that a NSCLP locus maps on 6p23 very close to D6S89. Results for D6S109 and D6S105 do not show a clear association. Differences observed between NSCLP-MX and Sx families seem to represent different etiologic entities. The results of the present study, plus those already published for candidate loci, TGFA and MSX1, support the hypothesis that several interacting major genes participate in the etiology of NSCLP