Lilia Maria de Azevedo Moreira

A síndrome de Down e sua patogênese: considerações sobre o determinismo genético

The analysis of causal factors for Down syndrome and its pathogenesis allows, beyond the analysis itself, a review of the natural history of the syndrome and the effects of the trisomy of 21q22 chromosome band which has been considered critical for the development of the disorder. Although there is always a chromosome imbalance in Down syndrome patients, the relevance of the genetic determinism can be questioned since DS subjects cognitive potential can be better developed through theearly intervention of neuro-motor and psycho-educational programs.

Idade materna e síndrome de Down no Nordeste do Brasil

This study analyzes the association between advanced maternal age and increased incidence of Down syndrome in neonates, based on a population sample from the State of Bahia in Northeast Brazil. Age of the mothers of 220 Down syndrome subjects was investigated, and age distribution was compared to that of the population control group, 220 mothers of subjects without Down syndrome. The proportion of Down syndrome infants dependent on advanced maternal age was estimated at 43.6%, thus showing a high correlation (r = 0.95) between advanced maternal age and Down syndrome incidence. However, this component was significantly lower than the 75% reported in the literature. The component independent of maternal age was estimated at 56.4%, indicating the action of other factors on meiotic non-disjunction associated with 21 trisomy. The results also indicate that despite the regional characteristics of Northeast Brazil, factors both dependent and independent of maternal age show the same distribution observed in Southeast Brazil, where extensive studies have been performed.

Aspectos genéticos e sociais da sexualidade em pessoas com síndrome de Down

Regarding sexuality of Down Syndrome (DS) subjects, parents and educators tend to refer to their non-sexual behavior, and to consider their relationships as based on either affection or aggressive attitudes. This paper reviews important studies about sexuality and reproduction of DS and perform an analysis of the risks involved in the procreation of DS subjects. A possible explanation for the absence of sexuality in DS lies on the fact that different levels of maturity and social adjustment are disregarded. Factors such as parental overprotection, lack of friendships, and social prejudice are barriers for these people to develop their sexualities. The risks of having DS children when both partners are DS and when only one of them is DS are presented here. In the first situation, if both partners are fertile, the probability is 50% of having a 21-trisomy conceptus, and 25% of having normal offspring. The percentage remaining corresponds to not viable 21 tetrasomy zygotes. The probability of a couple having normal children can be increased, however, to 50% when only one of the partners is DS. In cases of DS with 14/21 or 21/21 translocations, the probability of having normal children is also 50%. However, this probability can be reduced in DS with mosaicism. The right of ones person to live his/her sexuality, on one hand, and the high genetic risk of DS recurrence, on the other, show the need for further discussing this issue and providing emotional support as well as sexual education for DS subjects.

Evaluation of genotoxicity using the micronucleus assay and nuclear abnormalities in the tropical sea fish Bathygobius soporator (Valenciennes, 1837) (Teleostei, Gobiidae)

The micronucleus and nuclear abnormalities assays have been used increasingly to evaluate genotoxicity of many compounds in polluted aquatic ecossystems. The aim of this study is to verify the efficiency of the micronucleus assay and nuclear abnormality assay in field and laboratory work, when using erythrocytes of the tropical marine fish Bathygobius soporator as genotoxicity biomarkers. Gill peripheral blood samples were obtained from specimens of Bathygobius soporator. In order to investigate the frequencies of micronuclei and to assess the sensitivity of species, the results were compared with samples taken at the reference site and maintained in the laboratory, and fish treated with cyclophosphamide. The micronucleus assay was efficient in demonstrating field pollution and reproducing results in the labotatory. There were significant higher frequencies of micronuclei in two sites subject to discharge of urban and industrial effluents. The nuclear abnormality assay did not appear to be an efficient tool for genotoxicity evaluation when compared with field samples taken at a reference site in laboratory, with a positive control.

New studies of second and fourth digit ratio as a morphogenetic trait in subjects with congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is a disease that occurs during fetal development and can lead to virilization in females or death in newborn males if not discovered early in life. Because of this there is a need to seek morphological markers in order to help diagnose the disease. In order to test the hypothesis that prenatal hormones can affect the sexual dimorphic pattern 2D:4D digit ratio in individual with CAH, the aim of this study was to compare the digit ratio in female and male patients with CAH and control subjects.

Evidence against a Relationship between Dermatoglyphic Asymmetry and Male Sexual Orientation

Hall and Kimura (1994) studied the relation between dermatoglyphic asymmetry and male sexual orientation in a sample of 66 homosexual and 182 heterosexual men. They found that more homosexual men possessed a leftward dermatoglyphic asymmetry than did heterosexual men. In this paper, we report a comparative study about the relationship between sexual orientation and dermatoglyphic characteristics, including 60 homosexual men, 76 heterosexual men, and 60 heterosexual women, recruited from the general population, and also from a gay-rights nongovernmental organization, in Salvador, Brazil. Ulnar loops were the most frequent dermatoglyphic pattern in all groups, followed by whorls, arches, and radial loops. A chi-square analysis comparing the frequencies of the patterns in the three groups only showed an excess of ulnar loops in women (p < 0.05) and arches in men (p < 0.01), but did not reveal significant differences between homosexuals and the other groups studied. There was no significant difference between gay and straight men on total ridge count. We found a preponderance of rightward asymmetry in homosexual and heterosexual men, as well as in heterosexual women. Our results do not agree with Hall and Kimuras data indicating that more gay men possessed the minority leftward asymmetry than did straight men. There was no significant difference in leftward asymmetry in the sample studied. The results reported in this paper do not support any relation between dermatoglyphic asymmetry and male sexual orientation, and, thus, any hypothesis concerning a biological intrauterine contribution to adult sexual orientation somehow associated with dermatoglyphic development.

Long-term follow-up of four patients with langer–giedion syndrome: Clinical course and complications

Long‐term observations of individuals with the so‐called Langer–Giedion (LGS) or tricho–rhino‐phalangeal type II (TRPS2) are scarce. We report here a on follow‐up of four LGS individuals, including one first described by Andres Giedion in 1969, and review the sparse publications on adults with this syndrome which comprises ectodermal dysplasia, multiple cone‐shaped epiphyses prior to puberty, multiple cartilaginous exostoses, and mostly mild intellectual impairment. LGS is caused by deletion of the chromosomal segment 8q24.11–q24.13 containing among others the genes EXT1 and TRPS1. Most patients with TRPS2 are only borderline or mildly cognitively delayed, and few are of normal intelligence. Their practical skills are better than their intellectual capability, and, for this reason and because of their low self‐esteem, they are often underestimated. Some patients develop seizures at variable age. Osteomas on processes of cervical vertebrae may cause pressure on cervical nerves or dissection of cerebral arteries. Joint stiffness is observed during childhood and changes later to joint laxity causing instability and proneness to trauma. Perthes disease is not rare. Almost all males become bald at or soon after puberty, and some develop (pseudo) gynecomastia. Growth hormone deficiency was found in a few patients, TSH deficiency so far only in one. Puberty and fertility are diminished, and no instance of transmission of the deletion from a non‐mosaic parent to a child has been observed so far. Several affected females had vaginal atresia with consequent hydrometrocolpos.

Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies

Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype.

Longitudinal observation of a patient with Rieger syndrome and interstitial deletion 4 (q25–q31.1)

Rieger syndrome (RS; OMIM 180500) is a rare autosomal dominant disorder of morphogenesis, with ocular and systemic abnormalities and variability in phenotypic expression. Some patients with RS presented with a deletion of the band 4q25 to which the homeobox gene PIT X2 (former RIEG) was mapped. To study the natural history and perform a genotype–phenotype correlation, we followed a girl with RS from the age of 1 year to puberty. The study included physical examination, clinical and psychological evaluation, and cytogenetic analysis with GTG‐banded karyotype and array CGH. Additionally, molecular analysis using microsatellite markers for chromosome 4 (D4S427, D4S194 and D4S1615) was performed. Conventional chromosome analysis showed a 4q deletion, and aCGH confirmed the determination of the breakpoints at 4q25 and 4q31. With the exception of the typical features of RS is the patient, the clinical manifestations were relatively mild, despite the relatively large size of the deleted chromosome segment. The patient was periodically re‐evaluated for several years. The teeth are still abnormal, and she is still under orthodontic treatment. The facial features were attenuated with age. Currently, she is under constant monitoring of eye pressure. She benefited from early intervention program, and her tonus is normal. She attends a normal school with minor learning difficulties. In conclusion, this study offers a comprehensive phenotypic delineation of RS through almost two decades and may contribute to a more accurate genetic counseling in cases of this syndrome.

Diagnóstico laboratorial do albinismo oculocutâneo

OBJECTIVES: To evaluate the laboratories methods of the oculocutaneous albinism (OCA 1and OCA 2) of descriptive form and to analyze its results. METHODS: The hair bulb test is a chemical method used to distinguish the two forms, however, recently had its effectiveness as an standard test contested. The advance of molecular biology allows the analysis of the mutations that cause the disturb and its genic location. CONCLUSIONS: The bulb test is secure only for the diagnosis of OCA 1A, being able to be used as complement of a more refined method. The molecular analysis supplies a diagnostic definitive allowing to distinguish OCA 1 from OCA 2, because the mutations affect genes in different chromosomes.