Mucopolysaccharidosis type II: identification of 30 novel mutations among Latin American patients.

In this study, 103 unrelated South-American patients with mucopolysaccharidosis type II (MPS II) were investigated aiming at the identification of iduronate-2-sulfatase (IDS) disease causing mutations and the possibility of some insights on the genotype-phenotype correlation The strategy used for genotyping involved the identification of the previously reported inversion/disruption of the IDS gene by PCR and screening for other mutations by PCR/SSCP. The exons with altered mobility on SSCP were sequenced, as well as all the exons of patients with no SSCP alteration. By using this strategy, we were able to find the pathogenic mutation in all patients. Alterations such as inversion/disruption and partial/total deletions of the IDS gene were found in 20/103 (19%) patients. Small insertions/deletions/indels (<22 bp) and point mutations were identified in 83/103 (88%) patients, including 30 novel mutations; except for a higher frequency of small duplications in relation to small deletions, the frequencies of major and minor alterations found in our sample are in accordance with those described in the literature.

Effect of chromosome constitution variations on the expression of Turner phenotype.

Turner syndrome (TS) is a chronic disease related to haploinsufficiency of genes that are normally expressed in both X chromosomes in patients with female phenotype that is associated with a wide range of somatic malformations. We made detailed cytogenetic and clinical analysis of 65 patients with TS from the region of Recife, Brazil, to determine the effects of different chromosome constitutions on expression of the TS phenotype. Overall, patients with X-monosomy exhibited a tendency to have more severe phenotypes with higher morbidity, showing its importance in TS prognosis. Additionally, we found rare genetic and phenotypic abnormalities associated with this syndrome. To the best of our knowledge, this is the first case of 45,X,t(11;12)(q22;q22) described as a TS karyotype. Turner patients usually have normal intelligence; however, moderate to severe levels of mental retardation were found in 5 TS cases, which is considerate a very uncommon feature in this syndrome.

The influence of adsorption phenomena on the impedance spectroscopy of an electrolytic cell.

In this work we investigate the influence of the adsorption of ions on the impedance spectroscopy of an electrolytic cell. We consider that the positive and negative ions present in a dielectric liquid are adsorbed in the electrode surfaces with different adsorption energies. This difference in adsorption energies causes an additional plateaux in the limit of the low-frequency range of the real part of the impedance Z. In the same frequency range, a second minimum in the imaginary part of Z is predicted. The theory is illustrated with measurements of the impedance of an electrolytic solution in the frequency range from 10(-2) Hz to 1 KHz. A comparison between the present model and others from the literature to describe the experimental results is also made.

Identification of a de novo inv dup(X)(pter--> q22) by multicolor banding in a girl with Turner syndrome.

We report on a 23-year-old girl with short stature, short and wide neck, low posterior hairline, hypogonadism, underdeveloped breasts, infantile uterus, ovaries not visualized, and primary amenorrhea. Cytogenetic G-banding analysis revealed a mosaic karyotype of 46,X,dup(X)(q22)[35]/45,X[15], confirming the clinical suspicion of Turner syndrome. Molecular cytogenetics using a multicolor banding probe set for the X-chromosome characterized an inverted dup(X). The karyotype of the patient was therefore interpreted as 46,X,inv dup(X) (pter --> q22::q22 --> pter). This patient had a mosaic Turner syndrome with a cell line comprising partial trisomy Xpter to Xq22 and partial monosomy Xq22 to Xqter.

Dielectric dispersion of water in the frequency range from 10 mHz to 30 MHz.

We investigate the dielectric dispersion of water, specially in the low-frequency range, by using the impedance spectroscopy technique. The frequency dependencies of the real R and imaginary chi parts of the impedance could not be explained by means of the usual description of the dielectric properties of the water as an insulating liquid containing ions. This is due to the incomplete knowledge of the parameters entering in the fundamental equations describing the evolution of the system, and on the mechanisms regulating the exchange of charge of the cell with the external circuit. We propose a simple description of our experimental data based on the model of Debye, by invoking a dc conductivity of the cell, related to the nonblocking character of the electrodes. A discussion on the electric circuits able to simulate the cell under investigation, based on bulk and surface elements, is also reported. We find that the simple circuit formed by a series of two parallels of resistance and capacitance is able to reproduce the experimental data concerning the real and imaginary part of the electrical impedance of the cell for frequency larger than 1 Hz. According to this description, one of the parallels takes into account the electrical properties of interface between the electrode and water, and the other of the bulk. For frequency lower than 1 Hz, a good agreement with the experimental data is obtained by simulating the electrical properties of the interface by means of the constant phase element.

Clinical and biochemical studies in mucopolysaccharidosis type II carriers.

The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16-57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for non-carriers; there was, however, an overlap between carriers' and non-carriers' values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations.

[Down syndrome associated with clinical manifestations of Kabuki syndrome: report of a case] / Síndrome de Down associada a manifestações clínicas da síndrome Cabúqui: relato de um caso.

OBJECTIVE: To describe an atypical case of Down syndrome presenting with additional clinical manifestations that might be components of Kabuki (Niikawa-Kuroki) syndrome.CLINICAL REPORT: We report the clinical history of a 19-month-old girl with a 47,XX, +21 karyotype, who presented brachycephaly, flat face, long palpebral fissures, eversion of the lateral portion of the lower eyelids, arched eyebrows with sparse lateral regions, long eyelashes, epicanthus, cortical cataract, small ears, protruding tongue, muscular hypotonia, developmental delay, hyperflexibility of joints, brachydactyly, and dermatoglyphic abnormalities.CONCLUSION: The diagnosis of Down syndrome was confirmed cytogenetically. However, the presence of additional anomalies - mainly in the ocular region - suggested that the child might also have the Kabuki syndrome.

A new case of the acromegaloid facial appearance syndrome?

An apparently new case of the acromegaloid facial appearance syndrome is reported. The main clinical findings were coarse facies and thickened lips, oral mucosa and upper eyelids. The patient also had macrocephaly with an arachnoid cyst in the right middle fossa, an anomaly not previously described in association with this syndrome.

Oto-facio-osseous-gonadal syndrome: a new form of syndromic deafness?

In this study, we report on two brothers, born to consanguineous parents, with a syndrome of sensorineural deafness, short stature, cryptorchidism, inguinal hernia, brachycephaly, prominent forehead, flat face, downslanting palpebral fissures, low nasal root, hypoplastic alae and round tip to the nose, low-set prominent ears, narrow thorax, genu valgum, wormian bones, fusion of carpal bones, delayed bone age and congenital clubfeet. This combination of anomalies appears to be a previously undescribed syndrome, with probable autosomal recessive inheritance.

[Causes of pre-verbal deafness in an institutionalized population, emphasizing genetic etiology]. / Causas de surdez pré-verbal em uma população institucionalizada, enfatizando a etiologia genética.

OBJECTIVE: To investigate the causes of pre-verbal deafness in an institutionalized population emphasizing genetic etiology, considering the scarceness of national data in this field. METHODS: Based on the promptuaries of 658 pupils from 18 institutions for deaf people in Recife, information about audiological tests, laboratory examinations, etiology, associated anomalies, consanguinity and other deaf persons in the family was obtained; dysmorphologic examination was performed in 557 pupils; all the families with recurrent cases of deafness were investigated, having the pertinent pedigrees been constituted. RESULTS: About 13% of the studied population probably manifest genetic deafness; the autosomal recessive, autosomal dominant and X-linked recessive patterns of inheritance were observed, respectively, in 87.7%, 8.8% and 3.5% of the familial cases; among the examined pupils, 4.3% presented specific dysmorphic syndromes or anomalies associated with deafness; the acquired causes and unknown etiology were represented by 41.5% and 45.5% respectively. CONCLUSIONS: Obtained frequencies for the distinct causal factors of pre-verbal deafness are within the spectrum of variation of the frequencies observed in similar works, pointing out that in a great number of cases the etiology is unknown.

[Genetic deafness: a brief review]. / Surdez genética: uma revisão sucinta.

In this article, we present a brief literature review of hereditary deafness, considering the main historical aspects, genetic heterogeneity, gene mapping and the problems related to genetic counseling.