Case Report: A Case of a Patient with Smith-Magenis Syndrome and Early-Onset Parkinson's Disease.

Smith-Magenis Syndrome (SMS) is a rare genetic disorder, characterized by intellectual disability (ID), behavioral impairments, and sleep disturbances, as well as multiple organ anomalies in some affected individuals. The syndrome is caused by a deletion in the chromosome band around 17p11.2, including the Retinoic Acid Induced 1 (RAI1) gene, a multifaceted transcriptional regulator that modulates the expression of genes involved in cellular proliferation and neurodevelopment. This gene has a positive role in regulating BDNF and, importantly, affects several cell mechanisms and pathways such as the nigro-striatal pathway, which is crucial for motor function. Parkinson's disease (PD) is one of the most common neurodegenerative diseases in older populations. It is characterized by various physical symptoms including tremors, loss of balance, bradykinesia, and a stooping posture. We present a case study of a patient diagnosed with both SMS and early-onset PD (at the age of 49). The association between both conditions is as yet ambiguous. Genome-wide association studies (GWAS) implicate an association between the RAI1 gene and PD. Similarly, the co-existence of both SMS and PD in the patient suggests a possible association between RAI1 copy number variations (CNVs) and PD, further indicating that RAI1 has strong implications for PD pathogenesis. Our results suggest that RAI1 CNVs and the pathophysiology of PD may be related, underscoring the need for further research in this field. Therefore, caregivers of SMS patients should pay careful attention to the possibility of their patients developing EOPD and should consider starting treatment for PD as soon as the first symptoms appear.

Exploring an objective measure of overactivity in children with rare genetic syndromes.

BACKGROUND: Overactivity is prevalent in several rare genetic neurodevelopmental syndromes, including Smith-Magenis syndrome, Angelman syndrome, and tuberous sclerosis complex, although has been predominantly assessed using questionnaire techniques. Threats to the precision and validity of questionnaire data may undermine existing insights into this behaviour. Previous research indicates objective measures, namely actigraphy, can effectively differentiate non-overactive children from those with attention-deficit hyperactivity disorder. This study is the first to examine the sensitivity of actigraphy to overactivity across rare genetic syndromes associated with intellectual disability, through comparisons with typically-developing peers and questionnaire overactivity estimates. METHODS: A secondary analysis of actigraphy data and overactivity estimates from The Activity Questionnaire (TAQ) was conducted for children aged 4-15 years with Smith-Magenis syndrome (N=20), Angelman syndrome (N=26), tuberous sclerosis complex (N=16), and typically-developing children (N=61). Actigraphy data were summarized using the M10 non-parametric circadian rhythm variable, and 24-hour activity profiles were modelled via functional linear modelling. Associations between actigraphy data and TAQ overactivity estimates were explored. Differences in actigraphy-defined activity were also examined between syndrome and typically-developing groups, and between children with high and low TAQ overactivity scores within syndromes. RESULTS: M10 and TAQ overactivity scores were strongly positively correlated for children with Angelman syndrome and Smith-Magenis syndrome. M10 did not substantially differ between the syndrome and typically-developing groups. Higher early morning activity and lower evening activity was observed across all syndrome groups relative to typically-developing peers. High and low TAQ group comparisons revealed syndrome-specific profiles of overactivity, persisting throughout the day in Angelman syndrome, occurring during the early morning and early afternoon in Smith-Magenis syndrome, and manifesting briefly in the evening in tuberous sclerosis complex. DISCUSSION: These findings provide some support for the sensitivity of actigraphy to overactivity in children with rare genetic syndromes, and offer syndrome-specific temporal descriptions of overactivity. The findings advance existing descriptions of overactivity, provided by questionnaire techniques, in children with rare genetic syndromes and have implications for the measurement of overactivity. Future studies should examine the impact of syndrome-related characteristics on actigraphy-defined activity and overactivity estimates from actigraphy and questionnaire techniques.

Association of behavioural and social-communicative profiles in children with 16p11.2 copy number variants: a multi-site study.

BACKGROUND: Despite the established knowledge that recurrent copy number variants (CNVs) at the 16p11.2 locus BP4-BP5 confer risk for behavioural and language difficulties, limited research has been conducted on the association between behavioural and social-communicative profiles. The current study aims to further delineate the prevalence, nature and severity of, and the association between, behavioural and social-communicative features of school-aged children with 16p11.2 deletion syndrome (16p11.2DS) and 16p11.2 duplication (16p11.2Dup). METHODS: A total of 68 individuals (n = 47 16p11.2DS and n = 21 16p11.2Dup) aged 6-17 years participated. Standardised intelligence tests were administered, and behavioural and social-communicative skills were assessed by standardised questionnaires. Scores of both groups were compared with population norms and across CNVs. The influence of confounding factors was investigated, and correlation analyses were performed. RESULTS: Compared with the normative sample, children with 16p11.2DS showed high rates of social responsiveness (67%) and communicative problems (69%), while approximately half (52%) of the patients displayed behavioural problems. Children with 16p11.2Dup demonstrated even higher rates of social-communicative problems (80-90%) with statistically significantly more externalising and overall behavioural challenges (89%). In both CNV groups, there was a strong positive correlation between behavioural and social-communicative skills. CONCLUSIONS: School-aged children with 16p11.2 CNVs show high rates of behavioural, social responsiveness and communicative problems compared with the normative sample. These findings point to the high prevalence of autistic traits and diagnoses in these CNV populations. Moreover, there is a high comorbidity between behavioural and social-communicative problems. Patients with difficulties in both domains are vulnerable and need closer clinical follow-up and care.

Speech, Language, Hearing, and Otopathology Results From the International Smith-Magenis Syndrome Patient Registry.

PURPOSE: Smith-Magenis syndrome (SMS), a rare, genetically linked complex developmental disorder caused by a deletion or mutation within chromosome 17p11.2, is associated with delays in speech-language development, otopathology, and hearing loss, yet previous studies lack comprehensive descriptions of hearing and communication profiles. Here, analyses of patient registry data expand what is known about speech, language, hearing, and otopathology in SMS. METHOD: International speech-language and hearing registry survey data for 82 individuals with SMS were analyzed using descriptive and inferential statistics. Hearing loss, history of otitis media and pressure equalization (PE) tubes, communication mode, expressive/receptive language, and vocal quality were analyzed for all subjects and subjects grouped by age. Statistical methods included descriptive statistics and Pearson's chi-square tests of independence to test for differences between age groups for each variable of interest. Association analyses included Pearson's correlations. RESULTS: Hearing and otological analyses revealed that 35% of subjects had hearing loss, 66% had a history of otitis media, and 62% had received PE tubes. Speech-language analyses revealed that 60% of subjects communicated using speech, 79% began speaking words at/after 24 months of age, 92% combined words at/after 36 months, and 41% used sign language before speech. There was a significant association between the age that first words were spoken and the age that PE tubes were first placed. Communication strengths noted in more than 40% of subjects included social interest, humor, and memory for people, past events, and/or facts. CONCLUSIONS: Significant delays and impairment in speech-language were common, but the majority of those with SMS communicated using speech by age 6 years. Age was a significant factor for some aspects of hearing loss and communication. Neither hearing loss nor otitis media exacerbated language impairment. These results confirm and extend previous findings about the nature of speech, language, hearing, and otopathology in those with SMS.

Low-grade parental gonosomal mosaicism in CHD2 siblings with Smith-Magenis-like syndrome.

Loss-of-function CHD2 (chromodomain helicase DNA-binding protein 2) mutations are associated with a spectrum of neurodevelopmental disorders often including early-onset generalized seizures, photosensitivity, and epileptic encephalopathies. Patients show psychomotor delay/intellectual disability (ID), autistic features, and behavior disorders, such as aggression and impulsivity. Most reported cases are sporadic with description of germline mosaicism only in two families. We detect the first case of parental gonosomal CHD2 mosaicism disclosed by two brothers showing mild ID, born to healthy parents. The eldest brother has a history of drug-controlled generalized tonic-clonic seizures and displays sleep disorder and aggressive behavior suggestive of Smith-Magenis syndrome (SMS). Analysis of brothers' DNAs by next-generation sequencing (NGS) custom gene panel for pediatric epilepsy and/or ID disclosed in both the same pathogenic CHD2 variant. Additional NGS experiment on genomic DNA from parents' peripheral blood and from buccal swab raised the suspicion of low-grade gonosomal mosaicism in the unaffected mother subsequently confirmed by digital polymerase chain reaction (dPCR). This report underlines as worthwhile CHD2 screening in individuals presenting ID/developmental delay, with/without epilepsy, and behavior and sleep disorders suggestive of SMS. Detecting a CHD2 variant should prime testing probands' parents by NGS coupled to dPCR on different tissues to exclude/confirm gonosomal mosaicism and define the recurrence risk.

Comparative analyses of the Smith-Magenis syndrome protein RAI1 in mice and common marmoset monkeys.

Retinoic acid-induced 1 (RAI1) encodes a transcriptional regulator critical for brain development and function. RAI1 haploinsufficiency in humans causes a syndromic autism spectrum disorder known as Smith-Magenis syndrome (SMS). The neuroanatomical distribution of RAI1 has not been quantitatively analyzed during the development of the prefrontal cortex, a brain region critical for cognitive function and social behaviors and commonly implicated in autism spectrum disorders, including SMS. Here, we performed comparative analyses to uncover the evolutionarily convergent and divergent expression profiles of RAI1 in major cell types during prefrontal cortex maturation in common marmoset monkeys (Callithrix jacchus) and mice (Mus musculus). We found that while RAI1 in both species is enriched in neurons, the percentage of excitatory neurons that express RAI1 is higher in newborn mice than in newborn marmosets. By contrast, RAI1 shows similar neural distribution in adult marmosets and adult mice. In marmosets, RAI1 is expressed in several primate-specific cell types, including intralaminar astrocytes and MEIS2-expressing prefrontal GABAergic neurons. At the molecular level, we discovered that RAI1 forms a protein complex with transcription factor 20 (TCF20), PHD finger protein 14 (PHF14), and high mobility group 20A (HMG20A) in the marmoset brain. In vitro assays in human cells revealed that TCF20 regulates RAI1 protein abundance. This work demonstrates that RAI1 expression and protein interactions are largely conserved but with some unique expression in primate-specific cells. The results also suggest that altered RAI1 abundance could contribute to disease features in disorders caused by TCF20 dosage imbalance.

Speech and language characteristics in Smith–Magenis syndrome: Case report / Características del habla y del lenguaje en el síndrome de Smith-Magenis: caso clínico

Smith–Magenis syndrome (SMS) is a rare neurodevelopmental disorder with mild-to-moderate intellectual disability. Speech and language impairments have not been well described as part of the SMS phenotype. This study reports the speech and language characteristics presented by a classical SMS case, a 20-year-old woman with positive deletion in the region 17p11.2. The case presented a borderline IQ on verbal and performance Wechsler scales. Language standardized tests (i.e., Peabody, Token test, CEG test and Boehm test) and naturalistic language sample (i.e. conversation and story generation) were used to assess speech and language performance. Speech characteristics included imprecise speech, with a high speech rate, hoarse voice, hypernasality and intelligibility deficits. The performance in all standardized tests was poor. Socio-communicative deficits included repetitive and persistent verbal behavior, difficulties in the use of linguistic strategies to repair communication breakdowns, limited vocabulary production and short overall length utterances with reduced grammatical components. The results contribute to expanding knowledge about the SMS phenotype, also to highlight the need to include speech and language evaluation as part of the clinical assessment of SMS and, at the same time, to draw attention to the need to include early communications skills in language intervention programs.(AU)

El síndrome de Smith-Magenis (SMS) es un trastorno neuroevolutivo frecuente, que se caracteriza por la discapacidad intelectual de leve a moderada. Los trastornos del habla y del lenguaje no han sido bien descritos como parte del fenotipo del SMS. Este estudio reporta las características del habla y del lenguaje presentadas por un caso clásico de SMS, una mujer de 20 años de edad con deleción positiva en la región 17p11.2. El caso presentó un CI límite en las escalas verbales y de desempeño de Wechsler. Se utilizaron pruebas estandarizadas del lenguaje (pruebas de Peabody, Token, CEG y Boehm) y una muestra de lenguaje naturalista (es decir, conversación y generación de historias) para evaluar el desempeño del habla y del lenguaje. Las características del habla incluyeron imprecisiones, con una alta tasa de habla, voz ronca, hipernasalidad y déficits de inteligibilidad. Su desempeño fue malo en todas las pruebas estandarizadas. Los déficits socio-comunicativos incluyeron comportamiento verbal repetitivo y persistente, dificultades en el uso de estrategias lingüísticas para reparar los fallos de comunicación, producción de vocabulario limitado y longitudes de expresión cortas en general, con reducción de los componentes gramaticales. Los resultados ayudan a expandir el conocimiento sobre el fenotipo SMS, y también subrayan la necesidad de incluir la evaluación del habla y del lenguaje como parte de la evaluación clínica del SMS, y al mismo tiempo, atraer la atención sobre la necesidad de incluir competencias de comunicación temprana en los programas de intervención del lenguaje.(AU)

Clinical characteristics and genetic analysis of a neonate with Smith-Magenis syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic etiology for a neonate with Smith-Magenis syndrome (SMS).@*METHODS@#Copy number variation sequencing (CNV-seq) was applied to the neonate and his parents, and the genotype-phenotype correlation was analyzed.@*RESULTS@#On the second day after birth, the neonate had presented with pathological jaundice and immunodeficiency. Cranial MRI revealed ventricular enlargement and enlargement of cisterna magna. At 3 months, the infant has presented with square face, prominent forehead, deep-set eyes, hypertelorism, palpebral fissure upward and button noses. Genetic testing showed that he had carried a 2.9 Mb deletion in 17p11.2 region, seq[GRCh37] del(17)(p11.2)(chr17:16 836 379-19 880 992). The same deletion was not found in either parent.@*CONCLUSION@#SMS is mostly diagnosed in child and adulthood, but rarely in neonates. For neonates with SMS, the neurological and behavioral abnormalities have not been shown, but pathological jaundice, CNS abnormalities and immune deficiency may be the characteristics, which require attention of neonatal physicians.

Sleep disturbance associated with Smith-Magenis syndrome / 中华医学遗传学杂志

Smith-Magenis syndrome (SMS) (OMIM #182290) is a rare genetic disorder with a prevalence of 1 in 25 000 live births. Approximately 90% of SMS patients have harbored a 3.7 Mb interstitial 17p11.2 deletion involving the RAI1 gene, while 10% of cases have carried pathogenic variants of the RAI1 gene. SMS is characterized by sleep disturbance, intellectual impairment, developmental delay, craniofacial and cardiovascular anomalies, obesity, self injury, aggressive and autistic-like behaviors. Most SMS patients have sleep disorders such as short total sleep time, frequent night waking, short sleep onset, and early morning waking. The sleep disturbance may aggravate with age and persist throughout life. Three mechanisms have been delineated. The first concern was the abnormal secretion of melatonin, with high levels during daytime and low levels at night. Evaluation of the integrity of the intrinsically photosensitive retinal ganglion cell (ipRGC)/melanopsin system has found that SMS patients showed dysfunction in the sustained component of the pupillary light responses to blue light. Synchronization of daily melatonin profile and its photoinhibition are dependent on the activation of melanopsin. Dysfunction of the retina-melanin system may be one of the causes of melatonin spectrum disorders. Secondly, dysregulation of circadian rhythm gene expression has also been noted in mice and SMS patients. Finally, there may be association between sleep deprivation symptoms and DNA methylation patterns, which has provided new insights for SMS-associated sleep disorders and symptoms alike. Treatment for SMS-related sleep disorders is administered primarily through medications like melatonin tablets, which can alleviate insomnia-related sleep difficulties, in particular externalizing behavior in children. Researchers are also actively exploring other treatments for SMS currently.

Dental management for a child with smithmagenis syndrome under general anesthesia: case report

Introduction: Smith-Magenis Syndrome (SMS) is a genetic disease characterized by a neuro-behavioral deficiency caused by mutations or deletions at the 17p11.2 locus comprising the retinoic acid-induced 1 (RAI1) gene. The diagnosis is made through clinical analysis looking for characteristics and to prove this suspicion, a technique called Fluorescence In Situ Hybridization (FISH) is required. Objective: The aim of this case report is to be the first to describe the planning and execution of dental treatment for a 5yearold female patient with SMS under general anesthesia. Case report: The patient was admitted to the clinic of the Universidade Federal Fluminense, with possible dental pain, in the anamnesis the need for invasive treatment was observed in many dental elements and due to the patient's behavioral pattern, treatment under general anesthesia was chosen. Results: Procedures were performed (restorations and extractions) in the hospital in the same step. The child follow-up after the intervention every six month. Conclusion: SMS is a rare syndrome that requires extensive knowledge of the dentist and a detailed anamnesis to choose the best option to solve the case.

Introdução: A síndrome de Smith-Magenis (SMS) é uma doença genética caracterizada por uma deficiência neuro-comportamental causada por mutações ou deleções no locus 17p11.2 compreendendo o gene 1 induzido por ácido retinóico (RAI1). O diagnóstico é feito por meio de análises clínicas em busca de características e para comprovar essa suspeita, é necessária a técnica denominada Hibridização In Situ por Fluorescência (FISH). Objetivo: O objetivo deste relato de caso é o primeiro a descrever o planejamento e execução do tratamento odontológico para uma paciente do sexo feminino de 5 anos de idade com SMSsob anestesia geral. Relato do caso: O paciente deu entrada no ambulatório da Universidade Federal Fluminense, com possível dor dentária, na anamnese observou-se a necessidade de tratamento invasivo em diversos elementos dentais e devido ao padrão de comportamento do paciente optou-se pelo tratamentosob anestesia geral. Resultados: Os procedimentos foram realizados (restaurações e extrações) no hospital na mesma etapa. O acompanhamento da criança após a intervenção foi a cada seis meses. Conclusão: A SMS é uma síndrome rara que requer amplo conhecimento do dentista e uma anamnese detalhada para aescolha da melhor opção para a solução do caso.

El sueño del niño con trastornos del neurodesarrollo / The sleep in children with neurodevelopmental disorders

El sueño adecuado es necesario para el desarrollo sináptico y la maduración cerebral, un sueño de mala calidad tiene efectos perjudiciales en las funciones cognitivas, de atención, memoria y conducta de los niños. La preocupación sobre la alta prevalencia de los problemas del sueño es amplia en todo el mundo; las consecuencias de estos problemas son incluso más importantes en los niños portadores de trastornos del neurodesarrollo; estos niños a menudo tienen dificultades de inicio y mantenimiento del sueño y despertares nocturnos frecuentes que afectan a sus problemas de conducta. El propósito de este escrito es revisar el estado del arte de los problemas del sueño en los niños con trastornos del neurodesarrollo. En este punto, es importante tener en cuenta el ritmo circadiano, un reloj que genéticamente dirige los ritmos celulares de transcripción, traslación y metabolismos. Este reloj se combina con el ambiente diurno y nocturno coordinando estos mecanismos durante los ciclos luz/oscuridad, sueño/vigilia, frío/calor, ingesta/ayuno, tanto diariamente como en las diferentes estaciones. En conclusión, los problemas del sueño son un factor condicionante de la evolución y calidad de vida de los niños con trastornos del neurodesarrollo, que debe ser tenido en cuenta en todos los casos y ocupar un lugar preferente tanto en la etapa diagnóstica como en la terapéutica.

Adequate sleep is of critical need for a typical synaptic development and brain maturation, a poor quality sleep can have detrimental effects on children's' cognitive attention, memory, mood regulation, and behavior functions. Great concern has been voiced out regarding the high prevalence of poor sleep in children worldwide, the effects of poor sleep may be even more pronounced in children with neurodevelopmental disorders; these children often have difficulties with falling and staying asleep and with night awakenings, this has a strong association with daytime behavior problems. The purpose of this article is to provide an overview of the state of the science of sleep in children with a neurodevelopmental disorder. In this context, it is important to take the circadian cycle into account, a genetically encoded clock that drives cellular rhythms of transcription, translation and metabolism. The circadian clock interacts with the diurnal and nocturnal environment that also drives transcription and metabolism during light/dark, sleep/wake, hot/cold and feast/fast daily and seasonal cycles In conclusion, the sleep problems are a conditioning factor in the evolution and quality of life of children with neurodevelopmental disorders that must be taken into account in all cases and occupy a preferential place in both the diagnostic and the therapeutic stages.

Genetic diagnosis of a child with Smith-Magenis syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the molecular mechanism of a girl with developmental delay and intellectual disability.@*METHODS@#Chromosomal karotypes of the child and her parents were analyzed with routine G-banding method. Their genomic DNA was also analyzed with array comparative genomic hybridization (aCGH) for chromosomal duplications/deletions.@*RESULTS@#No karyotypic abnormality was detected in the child and her parents, while aCGH has identified a de novo 3.37 Mb deletion at 17p11.2 in the child.@*CONCLUSION@#The child was diagnosed with Smith-Magenis syndrome, for which RAI1 may be the causative gene.

Diagnosis of Smith-Magenis Syndrome in a Patient with Mental Retardation and Sleep Disturbance Confirmed by Multiplex Ligation-dependent Probe Amplification

No abstract available.

A Case of Smith-Magenis Syndrome with Multiple Organ Malformations

Smith-Magenis syndrome (SMS) is a genetic disease caused by microdeletion of p11.2 in chromosome 17. SMS patients have characteristic facial features and accompanying congenital malformations involving the brain, cardiovascular system, and urinary tract. Compared with the distinctive facial characteristics, organ malformations are less common. Several cases of SMS with tetralogy of Fallot have been reported in Korea, none of which were accompanied by other organ malformations. We present the first case report in Korea of an SMS patient with malformations of the brain, heart, and urinary tract.

Phenotypic and genetic analysis of a child carrying a 17q11.2 microdeletion / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a child with facial abnormalities with combined cytogenetic and molecular techniques and delineate its clinical phenotype.</p><p><b>METHODS</b>Neuropsychological profile of the child was analyzed. Color Doppler, CT and MRI were used for detecting the nodules in the body. Conventional peripheral blood karyotypes of the child and his parents were analyzed with G-banding. Array-comparative genomic hybridization (aCGH) was performed to detect minor structural chromosomal abnormalities.</p><p><b>RESULTS</b>The child had mental retardation, maxillofacial dysmorphism on the right side, and irregular solid nodules on the back. The karyotypes of the child and his parents were all normal, while aCGH has identified a de novo constitutive 1.2 Mb deletion at 17q11.2 in the child. The aCGH results of his parents were normal.</p><p><b>CONCLUSION</b>The de novo 17q11.2 microdeletion probably underlies the facial abnormalities and neurofibromatosis in the patient.</p>

Fisioterapia en el síndrome de Smith-Magenis: a propósito de un caso / Physiotherapy in Smith-Magenis syndrome: a case report

El síndrome de Smith-Magenis es una alteración del desarrollo psicomotor de origen genético, incluido en el grupo de enfermedades raras. En el caso clínico que se presenta, se realizó una valoración inicial de la coordinación, la marcha y el equilibrio a través del test de desarrollo psicomotor (TEPSI), un circuito diseñado específicamente, la prueba del tablero de clavijas de Purdue y el test Timed up and Go. Al finalizar los 3 meses que duró el tratamiento, basado en actividades de tipo lúdico, se realizó una valoración final con las mismas pruebas, encontrándose importantes diferencias objetivas en los resultados obtenidos, además de una mejoría subjetiva reportada por los padres del paciente. A pesar de que la evidencia sobre el tratamiento de fisioterapia en este síndrome es escasa, atendiendo a los resultados encontrados creemos que dicho tratamiento está totalmente justificado en el abordaje integral de los pacientes que lo padecen (AU)

The Smith-Magenis syndrome is a genetic psychomotor development disorder included in the group of rare diseases. In the clinical case presented, we performed an initial assessment of coordination, gait and balance using four different tests. These were psychomotor development test (TEPSI scale), Purdue pegboard, time up and go test, and a circuit designed specifically for this clinical case. At the end of the 3 months of treatment, and based on recreational type activities, a final assessment was made with the same tests. Significant objectives differences in the results as well as subjective improvement reported by the patient's parents were found. Although there is little evidence on physiotherapy treatment for this syndrome, in accordance with the results found, we believe that this treatment is totally justified in the comprehensive approach to patients suffering this disorder (AU)

Tecnología BACs-on-Beads™ aplicada al diagnóstico prenatal y al estudio citogenético de restos abortivos / BACs-on-Beads™ technology applied to prenatal diagnosis and the cytogenetic study of abortion remains

La tecnología de BACs-on-Beads utiliza sondas de ADN procedentes de Cromosomas Artificiales Bacterianos o BAC fijados en microesferas Luminex®. La muestra marcada y los ADN de referencia marcados se hibridan respectivamente con las mismas sondas BoBsTM complementarias. Después de la hibridación se leen las intensidades de la señal mediante el sistema instrumental Luminex® 100/200. Se puede aplicar al diagnóstico prenatal rápido con un kit diseñado para descartar aneuploidías para los cromosomas 13, 18, 21 y los cromosomas sexuales así como ganancias y pérdidas de ADN asociadas con 9 síndromes de microdeleción como son: Síndrome de DiGeorge, Síndrome de Williams-Beuren, Síndrome de Prader-Willi, Síndrome de Angelman, Síndrome de Smith-Magenis, Síndrome de Wolf-Hirschhorn, Síndrome de Cri du Chat, Síndrome de Langer-Giedion, y Síndrome de Miller-Dieker. Basados en esta misma tecnología se ha desarrollado un kit llamado KaryoLite-BoBsTM, que permite descartar aneuploidías para los 24 cromosomas y que se puede aplicar al estudio de alteraciones cromosómicas numéricas en restos abortivos. En este trabajo se presentan los resultados de nuestro grupo tras la aplicación de la tecnología de BAC-on-BeadsTM en 332 muestras de líquido amniótico, 48 muestras de vellosidades coriales y en el estudio de aneuploidías en 71 muestras de restos abortivos(AU)

BACs-on-Beads (BoBs) technology is based on DNA sequences from Bacterial Artificial Chromosomes fixed in Luminex® microspheres. The study sample and the reference DNA are labeled with similar but complementary BoBsTM probes. After the hybridisation, signal intensities were analysed using the Luminex® 100/200 instrumental system. This technology has been applied to rapid prenatal diagnosis with a kit designed to analyse aneuploidy for chromosomes 13, 18, 21 and sex chromosomes, and a panel of 9 microdeletion syndromes: DiGeorge, Williams-Beuren, Prader-Willi, Angelman, Smith-Magenis, Wolf-Hirschhorn, Cri du Chat, Langer-Giedion, and Miller-Dieker syndrome. Based on a similar technology, KaryoLite-BoBsTM kit allows the identification of aneuploidy for all 24 chromosomes, and can be applied to the analysis of products of conception, among other possibilities. In this study we present our current experience in the application of BAC-on-BeadsTM technology in 332 amniotic fluid samples; 48 chorionic villus samples and 71 samples from products of conception(AU)

Clinical and genetic study of a case with Smith-Magenis syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the clinical feature and genetic diagnosis for Smith-Magenis syndrome (SMS).</p><p><b>METHOD</b>The clinical data, including craniofacial anomalies, physical and mental status were analyzed. Routine and high resolution G-banding was performed to analyze the karyotype of the patient and her parents, and array comparative genomic hybridization (array CGH) was used to detect small chromosome anomaly.</p><p><b>RESULT</b>A-two-year old girl was sent to our clinic for mental retardation and cardiac malformation. Some sleep problems were reported by parents, including difficulties falling asleep, shortened sleep cycles. She also had some neurobehavioral symptoms including hyperactivity and self-injurious behaviors head-banging. She had distinctive craniofacial features including low hairline, frontal bossing, a broad face, broad nasal bridge, a tented upper lip, prognathism, low-set ears and high-vaulted arch. She had moderate mental retardation. Cardiac findings included ventricular septal defect, atrial septal defect, overriding aorta and pulmonary hypertension. Primary ventriculomegaly was seen in magnetic resonance imaging (MRI). Routine karyotype analysis showed a karyotype of 46, XX. However, high resolution karyotype analysis showed a suspected partial deletion of the short arm of chromosome 17. Array comparative genomic hybridization (array CGH) finely mapped the deletion to a 3.8 Mb region on 17p11.2. The molecular karyotype was then ascertained as 46, XX.arr17p11.2(16543655-20374751)×1dn. The parents had normal karyotypes.</p><p><b>CONCLUSION</b>Smith-Magenis syndrome is a multisystem disorder characterized by developmental delay and mental retardation, distinctive craniofacial features, sleep disturbance and behavioral problems. Array comparative genomic hybridization (array CGH) finely mapped the deletion on 17p11.2.</p>