In order to study the intra- and interspecific variability of the 14/15 association in Platyrrhini, we analyzed 15 species from 13 genera, including species that had not been described yet. The DNA libraries of human chromosomes 14 and 15 were hybridized to metaphases of Alouatta guariba clamitans, A. caraya, A. sara, Ateles paniscus chamek, Lagothrix lagothricha, Brachyteles arachnoides, Saguinus midas midas, Leontopithecus chrysomelas, Callimico goeldii, Callithrix sp., Cebus apella, Aotus nigriceps, Cacajao melanocephalus, Chiropotes satanas and Callicebus caligatus. The 14/15 hybridization pattern was present in 13 species, but not in Alouatta sara that showed a 14/15/14 pattern and Aotus nigriceps that showed a 15/14/15/14 pattern. In the majority of the species, the HSA 14 homologue retained synteny for the entire chromosome, whereas the HSA 15 homologue displayed fragmented segments. Within primates, the New World monkeys represent the taxon with the highest variability in chromosome number (2n = 16 to 62). The presence of the HSA 14/15 association in all species and subspecies studied herein confirms that this association is the ancestral condition for platyrrhines and that this association has been retained in most platyrrhines, despite the occurrence of extensive inter- and intrachromosomal rearrangements in this infraorder of Primates.

The Angelman syndrome (AS) (developmental delay, mental retardation, speech impairment, ataxia, outbursts of laughter, seizures) can result either from a 15q11-q13 deletion, or from paternal uniparental disomy (UPD), imprinting, or UBE3A mutations. We describe here the phenotypic and behavioral variability detected in eight UPD patients out of a group of 58 AS patients studied. All of them presented developmental delay, mental retardation, ataxia, speech impairment, and frequent drooling. Only one had microcephaly, whereas in two of them the OFC (head circumference) was above the 98th percentile. The weight of all patients was above the 50th percentile, and in three of them the height was above the 90th percentile. Three were able to say a few words and to communicate by gestures. Two patients presented hyperphagia, and three presented skin picking, common features in the Prader-Willi syndrome (PWS). Four patients (4/7) had wide-spaced teeth. Five presented seizures, and two others did not manifest frequent laughter. One patient was very different from the others, as he showed a better understanding and abilities to communicate, to play video games and to draw. We suggest here that there seems to be an extreme phenotypic and behavioral variability within the UPD group, and that both typical patients and those with mental retardation, language impairment, happy disposition, and hyperactivity should be tested for AS.

O segmento cromossômico 15q11-q13 é de grande interesse em Genética Humana uma vez que diversos rearranjos estruturais têm sido descritos nessa região (deleções, duplicações e translocações) resultando em fenótipos diferentes como os das síndromes de Prader-Willi (PWS) e Angelman (AS), que foram as primeiras doenças humanas a serem relacionadas com a expressão diferencial de alelos parentais (imprinting genômico). Contrário às leis de Mendel onde a herança parental da informação genética não influencia a expressão gênica, o imprinting genômico é caracterizado por modificações no DNA que produzem diferentes fenótipos dependendo da origem parental da mutação. A manifestação clínica da PWS aparece quando ocorre a perda de genes com expressão exclusivamente paterna, e a AS resulta da perda do gene com expressão exclusivamente materna. Diferentes mecanismos genéticos podem resultar em PWS ou AS como deleções, dissomia uniparental ou mutações no processo de imprinting. Em pacientes com AS existe uma classe adicional de pacientes com mutação no gene UBE3A. Estudos de pacientes com PWS e AS podem ajudar no entendimento do processo de imprinting e, assim, outras regiões do genoma com características similares podem ser localizadas, e diferentes síndromes podem ter seus mecanismos genéticos elucidados.

Chromosomal 15q11-q13 region is of great interest in Human Genetics because many structural rearrangements have been described for it (deletions, duplications and translocations) leading to phenotypes resulting in conditions such as the Prader-Willi (PWS) and Angelman (AS) syndromes which were the first human diseases found to be related to the differential expression of parental alleles (genomic imprinting). Contrary to Mendelian laws where the parental inheritance of genetic information does not influence gene expression, genomic imprinting is characterized by DNA modifications that produce different phenotypes depending on the parental origin of the mutation. Clinical manifestation of PWS appears when the loss of paternally expressed genes occurs and AS results from the loss of a maternally expressed gene. Different genetic mechanisms can lead to PWS or AS, such as deletions, uniparental disomy or imprinting mutation. In AS patients an additional class occurs with mutations on the UBE3A gene. Studies of PWS and AS patients can help us to understand the imprinting process, so that other genomic regions with similar characteristics can be located, and different syndromes can have their genetic mechanisms elucidated.

Os autores descrevem um caso típico de síndrome de Angelman. A paciente apresenta atraso de desenvolvimento neuropsicomotor, deficiência mental, macrostomia, dentes espaçados, convulsões, ausência de fala, andar com a base alargada e instável, crises de risos. Os estudos citogenéticos e moleculares revelaram deleção do segmento 15q11ql3 de origem materna, confirmando o diagnóstico clínico de síndrome de Angelman.

The authors describe the case of a typical Angelman syndrome patient. The proband presents developmental delay, mental retardation, macrostomia, wide-spaced teeth, seizures, absent speech, jerky gait, and paroxysms of laughter. The cytogenetic and molecular studies showed a maternal deletion of 15q11q13. These results are in agreement with the clinical diagnosis of Angelman syndrome.

Crianças com síndrome de Sotos apresentam aceleração do crescimento, macrocrania, padrões acromagalóides e dificuldades iniciais no desenvolvimento neuropsicomotor. A delineação da síndrome e o diagnóstico diferencial estão baseados na avaliação das características clínicas e no histórico evolutivo desses pacientes. Sete pacientes com síndrome de Sotos são descritos, bem como revistas as características clínicas presentes em 198 pacientes da literatura. As dificuldades motoras presentes durante a primeira infância nos pacientes com síndrome de Sotos são responsáveis pelo mau desempenho destas crianças nos testes de QI. A estimulação especializada deve ser encorajada para ajustar os afetados a superarem suas dificuldades iniciais.

Children with Sotos syndrome have growth acceleration, macrocephaly, acromegaloid features and delay in neuropsychomotor development during infancy. Syndrome delineation and differential diagnosis are based on evaluation of phenotypic characteristics and evolutive history of the patients. Seven patients with this syndrome are reported, and the relative occurrence of the phenotypic characteristics present in 198 reported cases are reviewed. Motor difficulties present in those patients during early infancy are responsible for the poor performance on IQ tests. Oriented stimulation should be encouraged in order to help the affected children to overcome their initial difficulties and to achieve normal scholarity and life performance.