Epidemiologic Features and Control Measures during Monkeypox Outbreak, Spain, June 2022.

During June 2022, Spain was one of the countries most affected worldwide by a multicountry monkeypox outbreak with chains of transmission without identified links to disease-endemic countries. We provide epidemiologic features of cases reported in Spain and the coordinated measures taken to respond to this outbreak.

An imported case of vaccine-derived poliovirus type 2, Spain in the context of the ongoing polio Public Health Emergency of International Concern, September 2021.

The monthly retrospective search for unreported acute flaccid paralysis (AFP) cases conducted as a complementary component of the Spanish AFP surveillance system identified a case of AFP in a child admitted in Spain from Senegal during August 2021. Vaccine-derived poliovirus 2 was identified in the stool in September 2021. We present public health implications and response undertaken within the framework of the National Action Plan for Polio Eradication and the Public Health Emergency of International Concern.

Anoctamin 5 (ANO5) muscular dystrophy-three different phenotypes and a new histological pattern.

OBJECTIVE: Anoctamin 5 (ANO5) is a putative intracellular calcium-activated chloride channel. Recessive mutations in ANO5 may present from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness. Here we describe the clinical, pathological, and molecular findings of three unrelated patients with ANO5-related muscular dystrophy. METHODS: In this retrospective study, we analyzed our database which includes 1700 muscle biopsies performed for diagnostic purposes from October 2004 to February 2019. Patients were attended by two myology experts, who performed and analyzed the muscle biopsies. Muscle biopsies were frozen in cooled isopenthane, cryostat sectioned, and routinely stained and reacted (minimum 16 stainings). A custom panel, including 115 genes (Nextera Rapid Capture, Illumina) and whole-exome sequencing analysis, was used for next-generation sequencing in cases without a definite pathological diagnosis. RESULTS: Three patients were diagnosed with ANO5-related muscular dystrophy, with all presenting the common exon 5 mutation c.191dup plus a compound heterozygous missense mutation. They showed three different phenotypes (distal myopathy, LGMD2L, and asymptomatic hyperCKemia). Curiously, all three muscle biopsies showed different patterns, but numerous ragged-red fibers with little endomysial inflammation and partial invasion cell by T lymphocytes were observed in one. CONCLUSION: ANO5-related muscular dystrophy is a heterogeneous disease with different clinical phenotypes as well as different histological patterns, which may even mimic a mitochondrial myopathy. The results of this study provide further knowledge of the clinical, histological, and pathological features related to ANO5 mutations.

Overview of Chromosome Abnormalities in First Trimester Miscarriages: A Series of 1,011 Consecutive Chorionic Villi Sample Karyotypes.

In order to contribute to the knowledge of type and frequency of chromosome abnormalities in early pregnancy losses, we analyzed the cytogenetic results from a large series of first trimester miscarriages, using a diagnostic approach with a high success rate and no maternal contamination. A total of 1,119 consecutive chorionic villi samples were obtained before evacuation, and karyotypes were prepared after short-term culture (STC). In 603 samples, a long-term culture (LTC) was also performed. The overall and individual frequencies of the different types of chromosome abnormalities were established, including placental mosaicisms, and their relationship with maternal age and gestational weeks was assessed. An abnormal karyotype was detected in 70.3% of the samples. Single autosomal trisomy was the most frequent abnormality (64.6% of the abnormal cases), followed by triploidy (13.1%) and monosomy X (10.4%). Chromosome rearrangements were found in 5.2%, combined abnormalities in 8.9%, and placental mosaicism in 3.5% of the cases with STC and LTC performed. Individual trisomies behaved differently with respect to maternal age and intrauterine survival. Due to the combination of STC and LTC, our study offers reliable information on the incidence and type of chromosome abnormalities and placental mosaicism in miscarriages and contributes to define the cytogenetic implication in their etiology.

A 92,XXXY Miscarriage Consecutive to a Digynic Triploid Pregnancy.

The patient was referred for prenatal diagnosis due to the sonographic finding of a polymalformed male fetus, and an amniocentesis was performed before termination of pregnancy. The pathological study of the placenta did not show morphological alterations. In her next pregnancy, sonographic examination disclosed a missed abortion with a visible embryo, and a chorionic villi sample was obtained for cytogenetic analysis before evacuation. Macroscopic examination of the villi sample did not reveal molar vesicular appearance. QF-PCR and cytogenetic analyses were performed on amniotic fluid (first pregnancy) and chorionic villi samples (second pregnancy). A 69,XXY and 92,XXXY karyotype was found, respectively. QF-PCR results disclosed 2 maternal and 1 paternal alleles in the first pregnancy (digynic triploidy), and double maternal and double paternal contribution to the tetraploid pregnancy. Among the few reported cases of 92,XXXY tetraploidy, those associated with partial moles show a PPPM genotype (3 paternal and 1 maternal alleles), and the only case with a PPMM genotype was found in a spontaneously aborted fetus similar to our case. We are not aware of other cases with combination of a digynic triploid pregnancy and a tetraploid pregnancy with a PPMM contribution. Our case adds evidence to the influence of the balance between paternal and maternal genomic doses on the phenotype.

Study of a fetal brain affected by a severe form of tyrosine hydroxylase deficiency, a rare cause of early parkinsonism.

Tyrosine hydroxylase (TH) deficiency is an inborn error of dopamine synthesis. Two clinical phenotypes have been described. The THD "B" phenotype produces a severe encephalopathy of early-onset with sub-optimal L-Dopa response, whereas the "A" phenotype has a better L-Dopa response and outcome. The objective of the study is to describe the expression of key synaptic proteins and neurodevelopmental markers in a fetal brain of THD "B" phenotype. The brain of a 16-week-old miscarried human fetus was dissected in different brain areas and frozen until the analysis. TH gene study revealed the p.R328W/p.T399M mutations, the same mutations that produced a B phenotype in her sister. After protein extraction, western blot analyses were performed to assess protein expression. The results were compared to an age-matched control. We observed a decreased expression in TH and in other dopaminergic proteins, such as VMAT 1 and 2 and dopamine receptors, especially D2DR. GABAergic and glutamatergic proteins such as GABA VT, NMDAR1 and calbindin were also altered. Developmental markers for synapses, axons and dendrites were decreased whereas markers of neuronal volume were preserved. Although this is an isolated case, this brain sample is unique and corresponds to the first reported study of a THD brain. It provides interesting information about the influence of dopamine as a regulator of other neurotransmitter systems, brain development and movement disorders with origin at the embryological state. This study could also contribute to a better understanding of the pathophysiology of THD at early fetal stages.

Montane and coastal species diversification in the economically important Mexican grasshopper genus Sphenarium (Orthoptera: Pyrgomorphidae).

The genus Sphenarium (Pyrgomorphidae) is a small group of grasshoppers endemic to México and Guatemala that are economically and culturally important both as a food source and as agricultural pests. However, its taxonomy has been largely neglected mainly due to its conserved interspecific external morphology and the considerable intraspecific variation in colour pattern of some taxa. Here we examined morphological as well as mitochondrial and nuclear DNA sequence data to assess the species boundaries and evolutionary history in Sphenarium. Our morphological identification and DNA sequence-based species delimitation, carried out with three different approaches (DNA barcoding, general mixed Yule-coalescent model, Bayesian species delimitation), all recovered a higher number of putative species of Sphenarium than previously recognised. We unambiguously delimit seven species, and between five and ten additional species depending on the data/method analysed. Phylogenetic relationships within the genus strongly support two main clades, one exclusively montane, the other coastal. Divergence time estimates suggest late Miocene to Pliocene ages for the origin and most of the early diversification events in the genus, which were probably influenced by the formation of the Trans-Mexican Volcanic Belt. A series of Pleistocene events could have led to the current species diversification in both montane and coastal regions. This study not only reveals an overlooked species richness for the most popular edible insect in Mexico, but also highlights the influence of the dynamic geological and climatic history of the region in shaping its current diversity.

Synthetic zinc finger repressors reduce mutant huntingtin expression in the brain of R6/2 mice.

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder caused by expanded CAG repeats in the huntingtin (HTT) gene. Although several palliative treatments are available, there is currently no cure and patients generally die 10-15 y after diagnosis. Several promising approaches for HD therapy are currently in development, including RNAi and antisense analogs. We developed a complementary strategy to test repression of mutant HTT with zinc finger proteins (ZFPs) in an HD model. We tested a "molecular tape measure" approach, using long artificial ZFP chains, designed to bind longer CAG repeats more strongly than shorter repeats. After optimization, stable ZFP expression in a model HD cell line reduced chromosomal expression of the mutant gene at both the protein and mRNA levels (95% and 78% reduction, respectively). This was achieved chromosomally in the context of endogenous mouse HTT genes, with variable CAG-repeat lengths. Shorter wild-type alleles, other genomic CAG-repeat genes, and neighboring genes were unaffected. In vivo, striatal adeno-associated virus viral delivery in R6/2 mice was efficient and revealed dose-dependent repression of mutant HTT in the brain (up to 60%). Furthermore, zinc finger repression was tested at several levels, resulting in protein aggregate reduction, reduced decline in rotarod performance, and alleviation of clasping in R6/2 mice, establishing a proof-of-principle for synthetic transcription factor repressors in the brain.

Nuchal translucency thickness in the prediction of unbalanced translocations.

OBJECTIVE: The aim of this study was to assess the role of nuchal translucency (NT) in the prediction of unbalanced translocation in offspring of couples in which one of the parents is a balanced translocation carrier. MATERIAL AND METHODS: From January 1996 to December 2012, fetal NT was measured before chorionic villus sampling in 86 pregnancies referred because of parental balanced translocation. RESULTS: No significant differences in pregnancy characteristics and in NT expressed in millimetres or in multiples of the median (MoMs) were observed between the 41 fetuses with a normal karyotype [1.72 mm, 95% confidence interval (CI): 1.49-1.96; 1.14 MoM; 95% CI: 1.01-1.26], the 38 fetuses with balanced translocations (1.78 mm, 95% CI: 1.44-2.12; 1.22 MoM; 95% CI: 1.01-1.43) and the 7 fetuses with unbalanced translocations (2.21 mm, 95% CI: 1.33-3.09; 1.59 MoM; 95% CI: 0.72-2.45). The proportions of fetuses with NT above 95th centile in the three groups were 9.1% in fetuses with normal karyotype, 18.4% in balanced translocations and 28.6% in unbalanced translocations, not significantly different. CONCLUSION: Although a trend to an increased NT was observed in fetuses with unbalanced translocation, no significant differences were reached. According to our results, a normal NT evaluation should not preclude the performance of CVS in pregnancies of balanced translocation parents.

[Eradication of poliomyelitis in Spain: What has happened in the last decade?] / Erradicación de la poliomielitis en España: ¿qué ha pasado en la última década?

On the 60th anniversary of the initiation of the polio vaccination campaign in Spain, the significant milestone in achieving disease control is highlighted. There has been a shift from an incidence of over 2,000 yearly cases in the 1960s to a sustained absence of wild poliovirus (WPV) since 1988. Despite the observed negative impact on polio vaccination coverage at the onset of the COVID-19 pandemic, these rates gradually recovered, reaching 98.2% in primary vaccination in 2022. Over the past decade, two essential elements have been identified to maintain the goal of polio elimination and that reinforces the importance of sustaining high vaccination coverage: robust epidemiological surveillance systems and a swift response to alerts to protect the vulnerable population and prevent virus reintroduction. In order to achieve eradication, it is crucial to interrupt international transmission and maintain continuous high-quality surveillance and effective coordination across different levels in response to any detection of PV, wild or vaccine derived. This article aimed to provide a comprehensive view of the polio eradication situation in Spain, focusing on the key events that occurred in the last decade and the present and future challenges.

hito en el control de la enfermedad que ha supuesto el cambio desde una incidencia de más de 2.000 casos anuales en la década de los 60 a una ausencia mantenida de poliovirus (PV) salvaje desde 1988. A pesar del impacto negativo observado en las coberturas de vacunación de poliomielitis al inicio de la pandemia de la COVID-19, estas se fueron recuperando, alcanzando un 98,2% en la primovacunación en 2022. En la última década se han identificado dos elementos esenciales para mantener el objetivo de eliminación de la poliomielitis y que, además, refuerzan la importancia de mantener altas coberturas de vacunación: los sistemas de vigilancia epidemiológica robustos y la respuesta rápida a las alertas para proteger a la población vulnerable y evitar la circulación del virus. Es crucial interrumpir la transmisión a nivel internacional para lograr la erradicación, manteniendo una vigilancia continua de alta calidad y una coordinación efectiva entre los diferentes niveles frente a cualquier detección de PV, ya sea salvaje o derivado de la vacuna. Este artículo tuvo como objetivo proporcionar una visión integral sobre la situación de erradicación de la poliomielitis en España, centrándose en los eventos clave ocurridos en la última década y en los retos presentes y futuros.

The Role of Heparin in Postural Orthostatic Tachycardia Syndrome and Other Post-Acute Sequelae of COVID-19.

The therapeutic management and short-term consequences of the coronavirus disease 2019 (COVID-19) are well known. However, COVID-19 post-acute sequelae are less known and represent a public health problem worldwide. Patients with COVID-19 who present post-acute sequelae may display immune dysregulation, a procoagulant state, and persistent microvascular endotheliopathy that could trigger microvascular thrombosis. These elements have also been implicated in the physiopathology of postural orthostatic tachycardia syndrome, a frequent sequela in post-COVID-19 patients. These mechanisms, directly associated with post-acute sequelae, might determine the thrombotic consequences of COVID-19 and the need for early anticoagulation therapy. In this context, heparin has several potential benefits, including immunomodulatory, anticoagulant, antiviral, pro-endothelial, and vascular effects, that could be helpful in the treatment of COVID-19 post-acute sequelae. In this article, we review the evidence surrounding the post-acute sequelae of COVID-19 and the potential benefits of the use of heparin, with a special focus on the treatment of postural orthostatic tachycardia syndrome.

Methylation screening of reciprocal genome-wide UPDs identifies novel human-specific imprinted genes.

Nuclear transfer experiments undertaken in the mid-80's revealed that both maternal and paternal genomes are necessary for normal development. This is due to genomic imprinting, an epigenetic mechanism that results in parent-of-origin monoallelic expression of genes regulated by germline-derived allelic methylation. To date, ∼100 imprinted transcripts have been identified in mouse, with approximately two-thirds showing conservation in humans. It is currently unknown how many imprinted genes are present in humans, and to what extent these transcripts exhibit human-specific imprinted expression. This is mainly due to the fact that the majority of screens for imprinted genes have been undertaken in mouse, with subsequent analysis of the human orthologues. Utilizing extremely rare reciprocal genome-wide uniparental disomy samples presenting with Beckwith-Wiedemann and Silver-Russell syndrome-like phenotypes, we analyzed ∼0.1% of CpG dinculeotides present in the human genome for imprinted differentially methylated regions (DMRs) using the Illumina Infinium methylation27 BeadChip microarray. This approach identified 15 imprinted DMRs associated with characterized imprinted domains, and confirmed the maternal methylation of the RB1 DMR. In addition, we discovered two novel DMRs, first, one maternally methylated region overlapping the FAM50B promoter CpG island, which results in paternal expression of this retrotransposon. Secondly, we found a paternally methylated, bidirectional repressor located between maternally expressed ZNF597 and NAT15 genes. These three genes are biallelically expressed in mice due to lack of differential methylation, suggesting that these genes have become imprinted after the divergence of mouse and humans.

Two new species of Melanoplus Stål, 1873 (Orthoptera: Acrididae: Melanoplinae) from northeastern Mexico.

Two new species of the genus Melanoplus Stål 1873 are described. M. trachodes n. sp., and M. parvus n. sp., both of which are endemic to the cool-temperate mountains of the Eastern Sierra Madre (ESM) in northeastern Mexico. Their habitat represents a transition zone between the ESM and the semiarid High Plateau Biogeographic provinces. This transition zone is characterized by an elevation range from 1,900 to 3,400 m and unique ecological conditions, which give rise to a considerable number of endemisms.

[Updated cost of vaccinating throughout life in Spain in 2023]. / Actualización del coste de vacunar a lo largo de toda la vida en España para el año 2023.

OBJECTIVE: Four modifications were introduced in the Lifetime Vaccination Schedule of the Interterritorial Council of the National Health System (CISNS) in 2023.The aim of this study was to estimate the cost of vaccinating a healthy person and people with certain risk conditions throughout life in Spain and to compare with a previous estimation from 2019. METHODS: A descriptive study of the cost of administering the vaccines included in the Lifetime Vaccination Schedule for the year 2023 and in the schedule for risk groups was carried out. RESULTS: The estimated cost to immunize a healthy person throughout life in 2023 is 1,541.56€ for a woman and 1,498.18€ for a men, which corresponds to an increase of 125% compared to the cost in 2019. The risk conditions with the highest cost are asplenia and complement deficiency and primary immunodeficiencies, with a cost of 3,159.82 euros and 2,566 euros respectively on average. The cost of vaccinating the whole healthy population in Spain in a year is around 565M€. Moreover, the cost of vaccinating the new-borns cohort of 2023 was estimated at 500M€. CONCLUSIONS: Despite the cost increase in 2023, immunization is still a very cheap intervention, considering the economic impact of immunopreventable diseases in the society. The relative low cost of immunization throughout life makes this health intervention useful and worthwhile.

OBJECTIVE: En el calendario de vacunación a lo largo de toda la vida del Consejo Interterritorial del Sistema Nacional de Salud (CISNS) se introdujeron cuatro modificaciones importantes en 2023. El objetivo de este estudio fue estimar el coste de la vacunación a lo largo de toda la vida a una persona sana y a ciertos grupos de riesgo tomando como referencia el calendario de 2023 y compararlo con una estimación previa de 2019. METHODS: Se realizo un estudio descriptivo del coste de administrar las vacunas incluidas en el calendario de vacunación a lo largo de toda la vida para el año 2023 y en el calendario para grupos de riesgo. RESULTS: El coste estimado de vacunar a una persona sana a lo largo de toda la vida en 2023 es de 1.541,56 euros en mujeres y 1.498,18 euros en hombres, lo que supondría un incremento del 125% con respecto al coste en 2019. Las condiciones de riesgo con el coste más alto son asplenia además de déficit del complemento e inmunodeficiencias primarias, suponiendo 3.159.82 euros y 2.566 euros, respectivamente, de media. Vacunar a toda la población sana en España en un año costaría unos 565 millones de euros y vacunar a la cohorte de recién nacidos de 2023 a lo largo de toda la vida unos 500 millones de euros. CONCLUSIONS: A pesar del incremento en el coste en 2023, considerando el impacto económico de las enfermedades prevenibles por vacunación en la sociedad, la vacunación sigue siendo una intervención barata que aporta múltiples beneficios.

Postural orthostatic tachycardia syndrome and other related dysautonomic disorders after SARS-CoV-2 infection and after COVID-19 messenger RNA vaccination.

The COVID-19 pandemic has caused a challenge for our society due to the post-acute sequelae of the disease. Persistent symptoms and long-term multiorgan complications, known as post-acute COVID-19 syndrome, can occur beyond 4 weeks from the onset of the COVID-19 infection. Postural orthostatic tachycardia syndrome (POTS) is considered a variety of dysautonomia, which is characterized by chronic symptoms that occur with standing and a sustained increase in heart rate, without orthostatic hypotension. POTS can lead to debilitating symptoms, significant disability, and impaired quality of life. In this narrative review, the etiopathogenic basis, epidemiology, clinical manifestations, diagnosis, treatment, prognosis, and socioeconomic impact of POTS, as well as other related dysautonomic disorders, after COVID-19 infection and SARS-CoV-2 postvaccination, were discussed. After a search conducted in March 2023, a total of 89 relevant articles were selected from the PubMed, Google Scholar, and Web of Science databases. The review highlights the importance of recognizing and managing POTS after COVID-19 infection and vaccination, and the approach to autonomic disorders should be known by all specialists in different medical areas. The diagnosis of POTS requires a comprehensive clinical assessment, including a detailed medical history, physical examination, orthostatic vital signs, and autonomic function tests. The treatment of POTS after COVID-19 infection or vaccination is mainly focused on lifestyle modifications, such as increased fluid and salt intake, exercise, and graduated compression stockings. Pharmacotherapy, such as beta-blockers, fludrocortisone, midodrine, and ivabradine, may also be used in selected cases. Further research is needed to understand the underlying mechanisms, risk factors, and optimal treatment strategies for this complication.

Implementation of Exome Sequencing in Clinical Practice for Neurological Disorders.

Neurological disorders (ND) are diseases that affect the brain and the central and autonomic nervous systems, such as neurodevelopmental disorders, cerebellar ataxias, Parkinson's disease, or epilepsies. Nowadays, recommendations of the American College of Medical Genetics and Genomics strongly recommend applying next generation sequencing (NGS) as a first-line test in patients with these disorders. Whole exome sequencing (WES) is widely regarded as the current technology of choice for diagnosing monogenic ND. The introduction of NGS allows for rapid and inexpensive large-scale genomic analysis and has led to enormous progress in deciphering monogenic forms of various genetic diseases. The simultaneous analysis of several potentially mutated genes improves the diagnostic process, making it faster and more efficient. The main aim of this report is to discuss the impact and advantages of the implementation of WES into the clinical diagnosis and management of ND. Therefore, we have performed a retrospective evaluation of WES application in 209 cases referred to the Department of Biochemistry and Molecular Genetics of the Hospital Clinic of Barcelona for WES sequencing derived from neurologists or clinical geneticists. In addition, we have further discussed some important facts regarding classification criteria for pathogenicity of rare variants, variants of unknown significance, deleterious variants, different clinical phenotypes, or frequency of actionable secondary findings. Different studies have shown that WES implementation establish diagnostic rate around 32% in ND and the continuous molecular diagnosis is essential to solve the remaining cases.

The effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage.

STUDY QUESTION: Is there any effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage? SUMMARY ANSWER: There was no significant difference in the chromosome abnormality rate between sporadic and recurrent miscarriage but the chromosome abnormality rate increased significantly with maternal age. WHAT IS KNOWN ALREADY: About 50-70% of non-recurrent miscarriages occur because of a chromosomal anomaly, but no agreement about the effect of either maternal age or the number of previous miscarriages on the chromosomal anomaly rate has been reached. STUDY DESIGN, SIZE, DURATION: A retrospective cohort of 353 miscarriages successfully karyotyped in the same center between 2002 and 2011, grouped according to the number of miscarriages and maternal age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the 353 women, 153 were below 35 years (73 with sporadic, 48 with two and 32 with recurrent miscarriage) and 200 were 35 years or more (81 with sporadic, 55 with two and 64 with recurrent miscarriage). The chromosomal anomaly rate and the anomaly spectrum were compared between sporadic and recurrent miscarriage, within the two maternal age groups, using the chi-square test and the Bonferroni correction for all the P-values. Risk of chromosomal anomaly was estimated for maternal age, number of miscarriages and previous live births by multivariate binary logistic regression analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Sporadic and recurrent miscarriage did not show significantly different chromosomal anomaly rates (68 versus 60%) and maternal age was the only statistically significant predictor of the chromosomal anomaly risk we identified. Some trends were observed in the chromosomal anomaly spectrum when sporadic was compared with recurrent miscarriage: recurrent miscarriage exhibited a decrease in viable trisomies (37 versus 11%) and an increase in non-viable trisomies (38 versus 57%) in women >35 years, together with an increase in unbalanced structural anomalies (4.9 versus 29%) in younger women. LIMITATION, REASONS FOR CAUTION: The mixed origin of our study population, and the limited number of recurrent miscarriages, particularly in the younger group, limits statistical power to detect differences. WIDER IMPLICATIONS OF THE FINDINGS: The most commonly observed chromosomal anomaly type in recurrent miscarriage depends on maternal age: non-viable autosomal trisomies in older women and unbalanced structural anomalies in younger women. When a chromosomal anomaly is identified as the cause of miscarriage, additional maternal evaluation may be avoided. STUDY FUNDING/COMPETING INTERESTS: No competing interests declared.

Familial 4.8 MB deletion on 18q23 associated with growth hormone insufficiency and phenotypic variability.

The deletion of the long arm of chromosome 18 causes a contiguous gene deletion syndrome with a highly variable phenotype, usually related to the extent of the deleted region. The most commonly reported clinical features include: decreased growth, microcephaly, facial abnormalities, hypotonia, developmental delay, intellectual disability, congenital aural atresia with hearing impairment and limb anomalies. Here we report on a familial terminal deletion of 18q23 region transmitted from a mother to two daughters, resulting in a remarkable phenotypic variability. The deletion was first detected by conventional cytogenetic analysis in one daughter and subsequently characterized using fluorescence in situ hybridization (FISH) and array-CGH. FISH analysis using subtelomeric 18p and 18q probes confirmed the 18qter deletion in the three patients, and FISH with a whole chromosome painting probe specific for chromosome 18 excluded rearrangements with other chromosomes. Array-CGH analysis allowed us to precisely define the extent of the deletion, which spans 4.8 Mb from 71,236,891 to 76,093,303 genomic positions and includes GALR1 and MBP genes, among others. High-resolution analysis of the deletion, besides a detailed clinical assessment, has provided important data for phenotype-genotype correlation and genetic counseling in this family. Furthermore, this study adds valuable information for phenotype-genotype correlation in 18q- syndrome and might facilitate future search for candidate genes involved in each phenotypic trait.

Fast protocol for the diagnosis of lysosomal diseases in nonimmune hydrops fetalis.

OBJECTIVE: Nonimmune hydrops fetalis (NIHF) is defined by the excessive fluid accumulation in more than one foetal compartments and body cavities because of nonimmune reasons. It has been described that 14 lysosomal diseases may be causative of NIHF. The aim of this study was to design a fast protocol to investigate the most frequent lysosomal diseases that are reported that may cause NIHF. METHOD: We analysed the glycosaminoglycans excretion in the amniotic fluid supernatant and four different lysosomal enzymatic activities in the amniotic cultured cells of the different NIHF amniotic fluids we received. RESULTS: We investigated 30 NIHF cases, using this fast protocol. We detected two cases of NIHF because of lysosomal diseases, which represent 6.6%. We diagnosed one case of mucopolysaccharidosis type VII and one case of Gaucher disease. CONCLUSION: The fast protocol we designed analyses seven of the most frequent lysosomal pathologies that have been described that may cause NIHF, with only five different determinations, which make the analysis of NIHF fast, cost-effective and without need of too much amniotic fluid. We believe this protocol may be useful for the analysis of lysosomal diseases in NIHF.