We describe a case of X monosomy associated with a maternally inherited t(13;14) Robertsonian translocation in a girl with Turner syndrome. The girl's X chromosome was demonstrated to be maternally inherited, ruling out the hypothesis that the translocation exerted an interchromosomal effect on the origin of the monosomy. Chromosomes 13 and 14 showed biparental inheritance. Key words: Robertsonian translocation, X monosomy, interchromosomal effect. It has been suggested that chromosomal rearrangements may disturb meiotic disjunction of chromosomes not involved in the rearrangement, resulting in an interchromosomal effect (Hamerton et al., 1968;Subri et al., 1980). We describe a case of X monosomy associated with a maternally inherited t(13;14) Robertsonian translocation in a girl with Turner syndrome. This study was approved by the ethics committee of our institution and informed consent was obtained from the parents of the girl.The five-year-old female proband was referred to our clinic because of short stature and facial dysmorphism. Clinical examination revealed short stature (< 2.5 percentile), weight between 2.5 and 10 percentile, flat frontal, large and prominent low-set ears, papebral ptosis, high nasal bridge, micrognathia, long philtrum, high palate, clinodactyly of the fifth left digit, and hypoplastic toe nails. Neuropsychological development was appropriate for the age. Chromosome analysis showed monosomy X and a Robertsonian balanced translocation -44,X,der(13;14) (q10;q10) karyotype. The girl's mother (who had a history of miscarriage) carried a balanced translocation but her father's karyotype was normal.To verify whether or not the Robertsonian translocation influenced non-disjunction of the X-chromosome, we determined the parental origin of the girl's X chromosome and normal chromosomes 13 and 14. Polymerase chain reaction was performed using DNA extracted from peripheral blood lymphocytes. We analyzed the CAG repeat on exon 1 of the X chromosome androgen receptor (AR) gene (Bharaj et al., 1999) and polymorphic markers on chromosome 13 (D13S787 and D13S895) and 14 (D14S592, D14S608 and D14S617). Our analysis showed both maternal inheritance of the X chromosome ( Figure 1) and biparental inheritance of chromosomes 13 and 14.Three previous cases of monosomy X associated with a t(13;14) translocation have been reported. Salamanca et al. (1985) reported a case of maternally inherited t(13;14) translocation but did not investigate the parental origin of the X-chromosome non-disjunction. Laszlo et al. (1984) reported the case of a patient, his mother and sister, who all had a t(13;14), but found no evidence of an interchromosomal effect. Krajinovic et al. (1994) found that both the X chromosome and the t(13;14) translocation in one of their patients were paternally inherited and thus demonstrated that the translocation had no effect on X chromosome non-disjunction. Kondo et al. (1979) compared the expected and observed frequency of the 45,X karyotype combined with unrelated balanced translocat...

Cleft lip and/or palate (CL/P) is a major congenital defect with complex etiology, including multiple genetic and environmental factors. Approximately two thirds of the cases are not accompanied by other anomalies and are called nonsyndromic (NS). In the present study, we performed transmission distortion analysis of the MSX1-CA, TGFB3-CA and MTHFR-C677T polymorphisms in 60 parent-child triads, in which the NS-CL/P affected child had at least one affected parent. No association with genes MSX1 or TGFB3 was found, but the results were suggestive of an association of the MTHFR-C677T polymorphism with NS-CL/P. Nonsyndromic cleft lip and/or palate (NS-CL/P) affect about 1/700 livebirths, with wide variability concerning geographic distribution, ethnic background and socioeconomic status (Murray, 2002). The etiology is complex, including multiple genetic and environmental factors. The MSX1 and TGFB3 genes have been suggested as candidate genes based on animal models (Satokata and Maas, 1994;Kaartinen et al., 1995;Proetzel et al., 1995) and association studies in humans with genes MSX1, TGFB3 and MTHFR have pointed to the involvement of these genes in NS-CL/P etiology (Maestri et al., 1997;Lidral et al., 1998;Romitti et al., 1999;Mills et al., 1999; Wyszynsky and Diehl, 2000;Beaty et al., 2001). The MSX1 gene maps to chromosome 4p16. Animal models indicate that this gene plays a role in craniofacial anomalies, leading to a clefting phenotype. Van den Boogaard et al. (2000) identified a stop codon in the MSX1 gene in a three-generation Dutch family with tooth agenesis and combinations of CP only and CLP, providing further evidence for the involvement of this gene in orofacial clefting. Jezewski et al. (2003) sequenced the whole MSX1 gene in a large sample of NS-CL/P patients from different geographic regions, and found mutations in about 2% of the cases.The TGFB3 gene maps to 14q24. Animal model studies demonstrated that TGFB3 plays a role in CP (Kaartinen et al., 1995;1997;Proetzel et al., 1995; Sanford et al., 1997), andLidral et al. (1998) showed an association between TGFB3 markers and NS-CP.The MTHFR gene maps to 1p36.1, and plays a key role in the metabolism of folate by reducing methylenetrahydrofolate to 5-methyltetrahydrofolate, the primary methyl donor for methionine synthesis. The C677T nucleotide variant in the MTHFR gene results in a thermally unstable protein with reduced activity, leading to elevated plasma homocysteine levels. Considerable heterogeneity in the prevalence of the C677T polymorphism throughout the world was reported (Pepe et al., 1998).The present work aimed to investigate if genes TGFB3, MSX1 and MTHFR-C677T are involved in the etiology of NS-CLP, by testing 60 patients, all with an affected parent. We utilized a nuclear family-based approach, to determine for each form of clefting whether these genes were in linkage disequilibrium, as measured by transmission distortion.A total of 60 triads, each one including an affected child and at least one affected parent, were studied. Of...