RESUMEN
OBJECTIVE: To estimate the prevalence of 35delG and Met34Thr variants in a Portuguese children's community sample and to compare these frequencies with nonsyndromic hearing-loss patients. METHODS: 502 children were randomly selected among the 8647 participants of the Portuguese birth cohort Generation XXI, and screened for Met34Thr and 35delG variants in the GJB2 gene. These variants were also studied on 89 index-cases, observed in the Clinic of "Hereditary Hearing-loss" in Saint John's Hospital Center, presenting a mild to profound nonsyndromic hearing-loss. RESULTS: Among the 502 children from Generation XXI, 10 were heterozygous for the 35delG variant (95% Confidence Interval 1.03-3.68) and 1 homozygous (95% Confidence Interval 0.01-1.24). Other 10 children presented heterozygosity for the Met34Thr variant (95% Confidence Interval 1.03-3.68). No homozygous for the Met34Thr or compound heterozygotes (35delG/Met34Thr) were found. In the total of 89 nonsyndromic hearing-loss patients, 5 (95% Confidence Interval 2.11-12.8) were heterozygous and 7 (95% Confidence Interval 3.61-15.6) were homozygous for the 35delG variant. The Met34Thr variant was found in 4 patients, 2 heterozygous (95% Confidence Interval 0.13-8.31) and 2 homozygous (95% Confidence Interval 0.13-8.31). CONCLUSION: The carrier frequency of 35delG and Met34Thr variants in a Portuguese sample was 1 in 50. Our data suggests that the 35delG mutation has an association with deafness. For the Met34Thr variant, no association was observed. However, Met34Thr seemed to conform to an additive model in hearing-loss.
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Conexinas/genética , Pérdida Auditiva/genética , Niño , Conexina 26 , Heterocigoto , Homocigoto , Humanos , Portugal , PrevalenciaRESUMEN
PURPOSE: To study the relationship of imprinted gene expression (CDKN1C, H19, IGF2, KCNQ1 and PHLDA2) with human fetal growth. METHODS: RNA was extracted from fetuses with intrauterine growth restriction (IUGR) and from the controls without growth restriction. The gene expression pattern of CDKN1C, H19, IGF2, KCNQ1 and PHLDA2 genes was evaluated using RT-PCR. MS-MLPA was also performed to assess the IC1 and IC2 DNA methylation status on chromosome 11p15.5. RESULTS: The samples were divided according to their tissue type in placental or fetal tissue. Within each group, IUGR cases and controls were compared. In the IUGR cases, in both fetal and placental tissue groups IGF2 was observed to be down regulated. In another approach, the samples were divided in IUGR and control groups and for each of them placental and fetal tissue was compared. Within the IUGR group up regulation of CDKN1C, KCNQ1, and PHLDA2 was determined in placental samples. IUGR group presented a statistically lower methylation status in both IC1 and in IC2. Regarding differences between fetal and placental samples within this group, methylation status of placental samples was statistically significant down regulated in the imprinting center 1 (IC1). CONCLUSIONS: Genomic imprinting is a phenomenon that plays an important role in fetal and placental development. This study emphasizes the importance of imprinted genes during pregnancy. Differences between tissues could reflect different mechanisms, either compensatory or adverse, that should be investigated in more detail.
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Inhibidor p57 de las Quinasas Dependientes de la Ciclina/genética , Desarrollo Fetal/genética , Impresión Genómica/genética , Factor II del Crecimiento Similar a la Insulina/genética , Canal de Potasio KCNQ1/genética , Proteínas Nucleares/genética , ARN Largo no Codificante/genética , Metilación de ADN/genética , Femenino , Retardo del Crecimiento Fetal/genética , Regulación del Desarrollo de la Expresión Génica/genética , Humanos , Placentación , EmbarazoRESUMEN
This article describes a patient with cryptorchidism and nonobstructive azoospermia presenting a novel microdeletion of approximately 1 Mb at 11p13. It was confirmed by multiplex ligation-dependent probe amplification that this heterozygous deletion spanned nine genes (WT1, EIF3M, CCDC73, PRRG4, QSER1, DEPDC7, TCP11L1, CSTF3 and HIPK3) and positioned the breakpoints within highly homologous repetitive elements. As far as is known, this is the smallest deletion as-yet described encompassing the WT1 gene and was detected only once in a total of 32 Portuguese patients with isolated uni- or bilateral cryptorchidism. These findings suggest that molecular analysis in patients with genitourinary features suggestive of WT1 impairment, namely cryptorchidism and renal abnormalities, may reveal cryptic genetic defects.