RESUMEN
Two common classes of deletions are described in the literature in individuals with Prader-Willi/Angelman syndrome (PWS/AS): one between breakpoint 1 (BP1) to BP3 and the other between BP2 to BP3 of the PWS/AS critical region on chromosome 15q11-->q13. We present here a novel observation of an approximately 253-kb deletion between BP1 and BP2 on 15q11.2, in a 3(1/2)-year-old boy, who was referred to us with a clinical suspicion of having Angelman syndrome and presenting with mental retardation, neurological disorder, developmental delay and speech impairment. Karyotype and FISH results were found to be normal. The microdeletion between BP1 and BP2 includes four genes - NIPA1, NIPA2, CYFIP1 and TUBGCP5 which was detected by a high-resolution oligonucleotide array-CGH that was further validated by a Multiplex Ligation-dependent Probe Amplification (MLPA) assay. The same deletion was observed in the father who presented with similar but relatively milder clinical features as compared to the affected son. Methylation studies by methylation-specific MLPA (MS-MLPA) of the SNRPN imprinting center (IC) showed a normal imprinting pattern, both in the patient and the father. To our knowledge a microdeletion limited only to the BP1-BP2 region has not yet been reported. The familial genetic alteration together with the striking clinical presentation in this study are interesting, but from our single case study it is difficult to suggest if the deletion is causative of some of the abnormal features or if it is a normal variant. The study however further strengthens the fact that genome-wide analysis by array CGH in individuals with developmental delay and mental retardation is very useful in detecting such hidden interstitial chromosomal rearrangements.
Asunto(s)
Síndrome de Angelman/genética , Eliminación de Gen , Enfermedades del Sistema Nervioso/genética , Síndrome de Prader-Willi/genética , Trastornos del Habla/genética , Preescolar , Mapeo Cromosómico , Metilación de ADN , Femenino , Impresión Genómica , Humanos , Hibridación Fluorescente in Situ , Masculino , Hibridación de Ácido Nucleico , Oligonucleótidos/química , LinajeRESUMEN
We have investigated the prevalence of mutations in the connexin 26 (GJB2) gene in Omani population using both PCR-RFLP and direct DNA sequencing methods. Two common GJB2 gene mutations (35delG and 167delT) were screened in 280 healthy controls and 95 deaf patients using two different PCR-RFLP methods. To investigate other GJB2 mutations, we have amplified and sequenced DNA from 51 unrelated deaf patients and 17 control subjects. None of the samples studied, either by RFLP or sequencing, revealed any deafness-associated mutations in the coding region of the GJB2 gene. These findings disagree with many reports on the GJB2 gene, describing various mutations as the cause of congenital recessive deafness. Although, an amino acid substitution (S86T) was identified by sequencing, we conclude that this change could not be associated with deafness since it was present in all the control and patient samples sequenced.
Asunto(s)
Conexinas/genética , Sordera/genética , Secuencia de Aminoácidos , Secuencia de Bases , Conexina 26 , ADN/química , ADN/genética , Análisis Mutacional de ADN , Humanos , Mutación , Omán , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
The aims of this study were to determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the United Arab Emirates (UAE), to describe the different mutations in the population, to determine its prevalence, and to study inheritance patterns in families of G6PD-deficient individuals. All infants born at Tawam Hospital, Al-Ain, UAE from January 1994 to September 1996 were screened at birth for their G6PD status. In addition, those attending well-baby clinics during the period were also screened for the disorder. Families of 40 known G6PD-deficient individuals, selected randomly from the records of three hospitals in the country, were assessed for G6PD deficiency. Where appropriate, this was followed by definition of G6PD mutations. Of 8198 infants, 746 (9.1%), comprising 15% of males and 5% of females tested, were found to be G6PD deficient. A total of 27 families were further assessed: of these, all but one family had the nt563 Mediterranean mutation. In one family, two individuals had the nt202 African mutation. The high manifestation of G6PD deficiency in women may be due to the preferential expression of the G6PD-deficient gene and X-inactivation of the normal gene, and/or to the presence of an 'enhancer' gene that makes the expression of the G6PD deficiency more likely. The high level of consanguinity which, theoretically, should result in a high proportion of homozygotes and consequently a higher proportion of females with the deficiency, was not found to be a significant factor.
Asunto(s)
Deficiencia de Glucosafosfato Deshidrogenasa/genética , Consanguinidad , Femenino , Pruebas Genéticas , Variación Genética , Genotipo , Glucosafosfato Deshidrogenasa/análisis , Deficiencia de Glucosafosfato Deshidrogenasa/epidemiología , Heterocigoto , Humanos , Recién Nacido , Masculino , Mutación , Linaje , Prevalencia , Emiratos Árabes Unidos/epidemiologíaRESUMEN
PCR-based typing of the HLA-DQA1 locus, using allele specific oligonucleotide (ASO) probes and reverse dot blot methodology was used to determine allelic distributions and construct a database for Arab and Pakistani individuals living in Dubai. Genotype and allelic frequencies were calculated, and the data were tested for departures from Hardy-Weinberg (HWE) equilibrium. The most frequent HLA-DQA1 alleles among Dubaian Arabs are DQA1 4 and 1.2. Among Pakistanis, the most frequent allele is also DQA1 4. No significant deviations from HWE were detected.
Asunto(s)
Árabes/genética , ADN/análisis , Frecuencia de los Genes/genética , Antígenos HLA-DQ/genética , Alelos , Manchas de Sangre , Medicina Legal , Marcadores Genéticos , Genotipo , Cadenas alfa de HLA-DQ , Humanos , Sondas de Oligonucleótidos/química , Pakistán/etnología , Emiratos Árabes Unidos/etnologíaRESUMEN
We studied 19 infants with a mean age of 3.8 months who presented with features consistent with acute lead encephalopathy following the use of traditional medicines. All presented with convulsions; CT scans of the brain on admission showed brain oedema in four, atrophy in four and normal findings in 11. Cerebrospinal fluid analysis in nine patients showed pleocytosis in six and a high protein content in eight. The median lead level in these 19 infants which encephalopathy was 3.6 mumol/l (74.5 micrograms/dl). Seven had a mean lead level of only 2.7 mumol/l (56.9 micrograms/dl) which is much below 70 micrograms/dl, the level usually proposed as the threshold for encephalopathy. Thirteen infants developed brain damage during follow-up; statistical analysis correlated the lead level at 2 months post chelation with an abnormal neurological outcome. Our findings indicate that in very young infants acute lead encephalopathy may occur at lead level lower than previously reported.
Asunto(s)
Encefalopatías/inducido químicamente , Intoxicación por Plomo/complicaciones , Encefalopatías/sangre , Encefalopatías/terapia , Desarrollo Infantil , Femenino , Humanos , Lactante , Plomo/sangre , Intoxicación por Plomo/sangre , Intoxicación por Plomo/terapia , Modelos Logísticos , Masculino , Medicina Tradicional , Estudios Retrospectivos , Factores de Riesgo , Emiratos Árabes UnidosRESUMEN
The aim of the study was to determine whether consanguineous marriages result in reproductive wastage and an increased incidence of illness in the offspring in a community with a long history of inbreeding and an expected high rate of consanguineous marriage. A representative sample of 2200 women aged > or = 15 years from Dubai and Al Ain, two cities in the United Arab Emirates, representing on the one hand a modern metropolis and on the other a traditional society, were studied. A questionnaire, which included questions on age, parity, gravidity, number of stillbirths, number of abortions, number of children alive, neonatal deaths and specific illnesses in children, was administered by nurses in antenatal and gynaecological clinics in the two cities. The rate of consanguineous marriage was 50.5% and parity, gravidity, ages and number of children were similar in consanguineous and non-consanguineous groups. There was no significant difference in rates of abortion, stillbirth and neonatal death between the two groups. Overall, there was statistically significant higher reproductive wastage in consanguineous couples, but when the category of less than second cousins was excluded from the consanguineous group no difference was found in reproductive wastage between consanguineous and non-consanguineous marriages. Children born to consanguineous unions also had significantly higher incidences of illnesses (37.1%) than those of non-consanguineous unions (29%). The occurrence of malignancies, congenital abnormalities, mental retardation and physical handicap was significantly higher in offspring of consanguineous than non-consanguineous marriages. In conclusion, consanguinity did not result in reproductive wastage, but was found to be an important factor in the causation of specific illnesses in offspring.
Asunto(s)
Consanguinidad , Enfermedades Genéticas Congénitas/epidemiología , Aborto Espontáneo/epidemiología , Adulto , Susceptibilidad a Enfermedades , Femenino , Muerte Fetal/epidemiología , Humanos , Persona de Mediana Edad , Embarazo , Emiratos Árabes Unidos/epidemiologíaRESUMEN
This study examines the frequency of consanguineous marriage and the coefficient of inbreeding in the United Arab Emirates (UAE). The study was conducted in Al Ain and Dubai cities between October 1994 and March 1995. A sample of 2033 married UAE females aged 15 years and over participated. The degree of consanguinity between each female and her spouse, and the degree of consanguinity between their parents were recorded. The rate of consanguinity in the present generation was high (50.5%) with a coefficient of inbreeding of 0.0222. The commonest type of consanguineous marriage was between first cousins (26.2%). Double first cousin marriages were common (3.5%) compared to other populations. The consanguinity rate in the UAE has increased from 39% to 50.5% in one generation. The level of consanguinity was higher in Al Ain (54.2%) than in Dubai (40%).
PIP: This study determines the extent of consanguinity within marriage among an urban population in the United Arab Emirates (UAE). Data were obtained during 1994-95 from interviews collected among a sample of 2200 married females over 15 years old from the cities of Al Ain and Dubai in the UAE. The sample was drawn with multistage sampling techniques from prenatal and gynecology clinics in Dubai and immunization centers in Al Ain. Marriages were grouped as: 1) double first cousin, 2) first cousin, 3) first cousin once removed, 4) second cousin, 5) less than first cousin, and 6) nonconsanguineous marriages. First cousin marriages were subgrouped as paternal and maternal types I and II (parallel cousins), and cross-cousin types III and IV. The median age of the sample was 25 years. 50.5% of the sample population had consanguineous marriages. The average coefficient of inbreeding (up to second cousin) was 0.0222. 26.2% of consanguineous marriages were first cousin marriages. 17% of total marriages were Type I, and 64.4% of first cousin marriages were Type I. 2.2% of all marriages were Type II, 3.2% were Type III, and 3.8% were Type IV. 3.5% were double first cousin marriages. 54.2% of marriages in Al Ain and 39.9% of marriages in Dubai were consanguineous. Al Ain had more double first cousin marriages (4.5% versus 0.56%). Dubai had more second cousin marriages (6.7% versus 1.6%). 28.2% were first cousin marriages in Al Ain, and 20.7% were first cousin marriages in Dubai. Type I was the most prevalent type of first cousin marriage in both cities, followed by Types IV, III, and II. The consanguinity rate was higher in the current generation than the parent generation (50.5% versus 39%), as was the coefficient of inbreeding (0.023 versus 0.0158). The increase in consanguinity was higher in Dubai. Consanguinity was higher in UAE than in Egypt, Syria, Lebanon, but about the same as in Jordan, Saudi Arabia, and Kuwait.
Asunto(s)
Consanguinidad , Matrimonio/etnología , Matrimonio/estadística & datos numéricos , Adulto , Femenino , Humanos , Masculino , Encuestas y Cuestionarios , Emiratos Árabes Unidos , Población UrbanaRESUMEN
The aim of this study was to explore the association between socio-demographic factors and consanguineous marriages in the United Arab Emirates (UAE). This was a cross-sectional population-based study conducted in the cities of Al Ain and Dubai between October 1994 and March 1995. A multi-stage sampling design was used and a representative total sample of 2,200 UAE females aged 15 years and above were included in this study. Data on 2,033 (85.8%) UAE national families who consented to participate in the study were obtained. The rate of consanguineous marriages in the sample was found to be 50.5% with 95% estimated population confidence limits 49.2-51.8%. The socio-demographic factors considered were: husband's age, wife's age, husband's and wife's educational levels, husband's occupation, wife's occupation, housing conditions, husband's parental kinship, wife's parental kinship, and kinship between the spouses. Consanguinity is more common among women with educated husbands (secondary or university/high) than among women with less educated husbands. The results indicate that the frequency of consanguineous marriages significantly increases when the husband's educational level is higher (p = 0.003). The distribution of relationship between spouses over the two generations of the study group and their parents is presented. The incidence of consanguineous marriages among the parents is 53% and 62% for the women and their husbands, respectively, and the overall incidence is 57%. The parallel patrilateral marriage is obviously the favoured practice when considering the parent's kinship distributions. The results of step-wise multiple logistic regression analysis for the occurrence of consanguineous marriages show that the husband's education and husband's parent's consanguinity status only are significantly associated variables.
Asunto(s)
Consanguinidad , Adulto , Escolaridad , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Emiratos Árabes UnidosAsunto(s)
Sarcoma Histiocítico/genética , Proteinosis Alveolar Pulmonar/genética , Médula Ósea/patología , Sarcoma Histiocítico/patología , Humanos , Lactante , Enfermedad de los Legionarios/patología , Masculino , Infecciones Oportunistas/patología , Neumonía por Pneumocystis/patología , Proteinosis Alveolar Pulmonar/patología , Alveolos Pulmonares/patologíaRESUMEN
Six infants, three of them neonates, were diagnosed as having acute lead poisoning; four of them had acute encephalopathy. All had been given an indigenous preparation, 'Bint Al Zahab' (Daughter of Gold), for abdominal colic and early passage of meconium after birth. Chemical analysis of this powder revealed a lead content of 82.5%. The index case had anaemia with punctate basophilia, dense metaphysial lines on X-ray and markedly raised blood lead levels, arousing a strong index of suspicion for the early diagnosis of subsequent cases. Computerized axial tomography (CAT) scan in three cases showed signs of early cerebral cortical atrophy. The picture of cerebral oedema was absent in the four cases of acute lead encephalopathy. The importance of prevention and the ideal management is discussed.