A case of Congenital disorder of glycosylation due to SSR4 gene deletion / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and molecular characteristics of a child with Congenital disorders of glycosylation (CDG).@*METHODS@#A 4-month-old boy who had presented at the Children's Hospital Affiliated to Zhejiang University Medical School on December 31, 2019 due to feeding difficulties after birth was selected as the study subject. High-throughput sequencing was carried out for the patient, and real-time qPCR was used for validating the suspected deletion fragments and the carrier status of other members of his family.@*RESULTS@#High-throughput sequencing revealed that the child had lost the capture signal for chrX: 153 045 645-153 095 809 (approximately 50 kb), which has involved 4 OMIM genes including SRPK3, IDH3G, SSR4 and PDZD4. qPCR verified that the copy number in this region was zero, while that of his elder brother and parents was all normal.@*CONCLUSION@#The deletion of the fragment containing the SSR4 gene in the Xq28 region probably underlay the SSR4-CDG in this child.

Clinical Analysis of Matched Sibling Donor Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Young Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of young patients with multiple myeloma (MM).@*METHODS@#The clinical data of 8 young patients (median age：46 years) with MM who underwent allo-HSCT from HLA-indentical sibling donors in the First Affiliated Hospital of Chongqing Medical University from June 2013 to September 2021 were collected, and their survival and prognosis were retrospectively analyzed.@*RESULTS@#All the patients were successfully transplanted, and 7 patients could be evaluated the efficacy after transplantation. The median follow-up time was 35.2 (2.5-84.70) months. The complete response (CR) rate was 2/8 before transplantation and 6/7 after transplantation. Acute GVHD developed in 2 cases and extensive chronic GVHD developed in 1 case. Within 100 days, 1 case died of non-recurrent events, and 1-year and 2-year disease-free survival were 6 and 5 cases, respectively. At the end of follow-up, all the 5 patients who survived for more than 2 years survived, and the longest disease-free survival time has reached 84 months.@*CONCLUSION@#With the development of new drugs, HLA-matched sibling donor allo-HSCT may be a curable treatment for young patients with MM.

Application of Microhaplotypes in Sibling Kinship Testing / 法医学杂志

OBJECTIVES@#To investigate the efficacy of different numbers of microhaplotype (MH) loci and the introduction of different reference samples on the identification of full sibling, half sibling and differentiation between full sibling and half sibling kinships, and to explore the effect of changing mutation rate on sibling testing.@*METHODS@#First, a family map involving three generations was established, and four full sibling identification models, five half sibling identification models and five models distinguishing full and half siblings were constructed for different reference samples introduced. Based on the results of the previous study, two sets of nonbinary SNP-MH containing 34 and 54 loci were selected. Based on the above MH loci, 100 000 pairs of full sibling vs. unrelated individuals, 100 000 pairs of half sibling vs. unrelated individuals and 100 000 pairs of full sibling vs. half sibling were simulated based on the corresponding sibling kinship testing models, and the efficacy of each sibling kinship testing model was analyzed by the likelihood ratio algorithm under different thresholds. The mutant rate of 54 MH loci was changed to analyze the effect of mutation rate on sibling identification.@*RESULTS@#In the same relationship testing model, the systematic efficacy of sibling testing was positively correlated with the number of MH loci detected. With the same number of MH loci, the efficacy of full sibling testing was better than that of uncle or grandfather when the reference sample introduced was a full sibling of A, but there was no significant difference in the identification efficacy of the four reference samples introduced for full sibling and half sibling differentiation testing. In addition, the mutation rate had a slight effect on the efficacy of sibling kinship testing.@*CONCLUSIONS@#Increasing the number of MH loci and introducing reference samples of known relatives can increase the efficacy of full sibling testing, half sibling testing, and differentiation between full and half sibling kinships. The level of mutation rate in sibling testing by likelihood ratio method has a slight but insignificant effect on the efficacy.

Calculation of Likelihood Ratios for Incest Cases Using IBD Patterns / 法医学杂志

OBJECTIVES@#To calculate the likelihood ratios of incest cases using identity by descent (IBD) patterns.@*METHODS@#The unique IBD pattern was formed by denoting the alleles from the members in a pedigree with a same digital. The probability of each IBD pattern was obtained by multiplying the prior probability by the frequency of non-IBD alleles. The pedigree likelihoods of incest cases under different hypotheses were obtained by summing all IBD pattern probabilities, and the likelihood ratio(LR) was calculated by comparing the likelihoods of different pedigrees.@*RESULTS@#The IBD patterns and the formulae of calculating LR for father-daughter incest and brother-sister incest were obtained.@*CONCLUSIONS@#The calculations of LR for incest cases were illustrated based on IBD patterns.

General Formulas for Calculating Commonly Used Kinship Index / 法医学杂志

OBJECTIVES@#To derive general formulas for calculating commonly used kinship index (KI).@*METHODS@#By introducing the Kronecker symbol, the formulas used to calculate the same KI under different genotype combinations were summarized into a unified expression.@*RESULTS@#The general formulas were successfully derived for KI in various case situations, including the paternity index, full sibling index, half sibling index, avuncular index, grandpaternity index, first-cousin index, and second-cousin index between two individuals without or with the mother being involved; grandpaternity index between grandparents and a grandchild without or with the mother being involved; half sibling index between two children with two mothers being involved; full sibling index among three children; and half sibling index among three children with no, one, or two mothers being involved.@*CONCLUSIONS@#The general formulas given in this study simplify the calculation of KIs and facilitate fast and accurate calculation through programming.

Identification Strategy of Biological Half Sibling Relationship / 法医学杂志

OBJECTIVES@#To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and to provide a reference for the setting of relevant standards for identification of half sibling relationship.@*METHODS@#(1) Based on the same genetic marker combinations, the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score (CIBS) and combined full sibling index in actual cases with the distributions in simulated cases. (2) In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters, were calculated. (3) The application value of LR method was compared with that of IBS method, by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. (4) According to the existing simulation data, the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting.@*RESULTS@#(1) After the rank sum test, under the premise that the real relationship and the genetic marker combination tested were the same, there was no significant difference between the simulation method and the results obtained in the actual case. (2) In most cases, under the same conditions, the system effectiveness obtained by LR method was greater than that by IBS method. (3) According to the existing data, the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99.@*CONCLUSIONS@#When distinguishing half sibling from full sibling pairs or unrelated pairs, it is recommended to give preference to the LR method, and estimate the required number of markers according to the identification types and the population data, to ensure the identification effect.

Analysis of Trio Half Sibling Testing / 法医学杂志

OBJECTIVES@#To establish an analytical method for half sibling testing involving common three relatives' participation.@*METHODS@#Based on the half sibling testing scenarios with the known biological mother, grandfather or uncle, and two unidentified controversial half siblings participating, two opposing hypotheses were set. Lineage reconstruction according to Mendel's law of heredity was carried out, and the calculation formula of the half sibling kinship index was derived. Verification of actual cases was carried out and the results were compared with duo half sibling testing.@*RESULTS@#In the scenarios of the known biological mother, grandfather and uncle participating in half sibling testing, the kinship calculation formulae of 54, 91 and 99 genotype combinations for kinship index calculation were deduced respectively. The actual cases showed higher kinship indexes in trio half sibling testing compared with duo half sibling testing.@*CONCLUSIONS@#It is beneficial to obtain more genetic information for family reconstruction and improvement of the strength of genetic evidence for half sibling testing by adding known relatives.

Evaluation of Detection Efficiency for Trio Full Sibling Testing / 法医学杂志

OBJECTIVES@#To study the detection efficiency of trio full sibling with another known full sibling reference added under different number of autosomal STR typing systems.@*METHODS@#Based on 43 detection systems consisting of 13 to 55 representative autosomal STR loci, 10 000 true families (full sibling group) and 10 000 false families (unrelated individual group) were randomly simulated. The full sibling index (FSI) was calculated based on the method of family reconstruction. The cumulative sibling relationship index (CFSI) of 0.000 1 and 10 000 were used as the evaluation thresholds, and the detection efficiency parameters were calculated and compared with the identification of the duo full sibling testing.@*RESULTS@#With the increasing number of STR loci, the error rate and inability of judgement rate gradually decreased; the sensitivity, specificity, correct rate of judgment and other parameters gradually increased, and the system efficiency gradually improved. Under the same detection system, trio full sibling testing showed higher sensitivity, specificity, system efficiency and lower inability of judgement rate compared with duo full sibling testing. When the system efficiency was higher than 0.85 and inability of judgement rate was less than 0.01%, at least 20 STRs should be detected for trio full sibling testing, which was less than 29 STRs required by duo full sibling testing.@*CONCLUSIONS@#The detection efficiency of trio full sibling testing is superior to that of duo full sibling testing with the same detection system, which is an effective identification scheme for laboratories with inadequate detection systems or for materials with limited conditions.

Efficiency Analysis of Uncle-Nephew Relationship Identification by Increasing STR Markers and Adding Reference Samples / 法医学杂志

OBJECTIVES@#To estimate the system efficiency of uncle-nephew relationship identification by increasing STR markers and adding reference samples based on the test results of simulated data and real samples, so as to provide references for selecting the appropriate number of STRs and reference samples for uncle-nephew relationship identification.@*METHODS@#Five common models of uncle-nephew relationship identification were constructed by adding different reference samples. In each model, the likelihood ratio (LR) for 10 000 pairs of uncle-nephew relationships and 10 000 pairs of unrelated individuals were simulated by detecting 19, 39 or 55 STRs, and the system efficiency at different thresholds was simulated. The samples of the Han population in Zhejiang were collected, and 55 autosomal STRs were obtained by using SiFaSTRTM 23plex kit, Goldeneye® DNA ID 22NC kit and AGCU 21+1 PCR amplification kit. When 19, 39 and 55 STRs were detected, the LR of each model and system efficiency under different thresholds were calculated and compared with the simulation results.@*RESULTS@#Under the same detection system, the calculated results of simulated data and corresponding true samples were basically consistent. In the same model, there was a positive correlation between the system efficiency of uncle-nephew relationship identification and the number of STRs detected. Moreover, the system efficiency of introducing relatives was higher than identifying only two individuals. The order of preference for the introduction of relatives was the full sibling (or mother) of the uncle and the full sibling (or mother) of the nephew.@*CONCLUSIONS@#The system efficiency of uncle-nephew relationship identification could be improved by increasing the number of STRs and introducing known relatives, which would provide the basis for selecting the most appropriate detection system and reference individuals in actual cases.

A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia / 中华血液学杂志

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .

Visita à criança hospitalizada em terapia intensiva: vivências de irmãos reveladas por meio do brinquedo terapêutico dramático / Visita al niño hospitalizado en terapia intensiva: vivencias de hermanos revelado por el juego terapéutico dramático / Visiting a hospitalized child in intensive care: experiences of siblings revealed through the dramatic therapeutic play

Resumo Objetivo: compreender, por meio do brinquedo terapêutico dramático, o significado, para o irmão, de visitar a criança hospitalizada em terapia intensiva. Método: pesquisa qualitativa, modalidade fenomenológica, que utilizou o brinquedo terapêutico dramático para acessar às experiências dos irmãos. Foi realizada em Unidade de Terapia Intensiva Pediátrica do interior do estado de São Paulo, Brasil. Participaram das sessões de brinquedo terapêutico 11 irmãos menores de 10 anos, as quais foram analisadas à luz da Teoria do Amadurecimento. Resultados: os irmãos, tendo um lugar para brincar, dramatizaram situações, anteriormente, vividas, de seu cotidiano e da visita à criança hospitalizada. Ao viver, criativamente, revelaram que brincar é fazer a integração das experiências do "eu", favorecendo o continuar a ser diante da situação vivida. Conclusões e implicações para a prática: o Brinquedo Terapêutico Dramático compreendido à luz de um referencial teórico possibilitou que o irmão significasse a visita como uma experiência de integração do "eu", revelando emoções, desejos e preferências do cotidiano. Nesse sentido, o cuidado ao irmão da criança hospitalizada define-se pela oferta do brincar livre, para que ele demonstre o sentimento de continuar a ser em suas interações com o mundo, no qual o contexto hospitalar tornou parte da realidade.

Resumen Objeto: Comprender por medio del juego terapéutico dramático el significado, para el hermano, de la visita al niño hospitalizado en Terapia Intensiva Pediátrica. Método: Investigación cualitativa, modalidad fenomenológica, que utilizó el juego terapéutico dramático para comprender la experiencia del hermano. Se realizó en Unidad de Terapia Intensiva Pediátrica del interior del Estado de São Paulo, Brasil. Participaron de las sesiones de juego terapéutico 11 hermanos con menos de 10 años, quienes fueron analizados a la luz de la Teoría de la Maduración. Resultados: Los hermanos, al tener un lugar para jugar, dramatizaron situaciones anteriormente vividas, de su cotidiano y de la visita al niño hospitalizado. Al vivir de forma creativa, revelaron que jugar es permitir la integración de las experiencias del "yo", lo que favorece el concepto de seguir siendo, ante la situación vivida. Conclusiones e implicaciones para la práctica: El Juego Terapéutico Dramático comprendido a la luz de un referencial teórico hizo posible que el hermano entendiera la visita como una experiencia de integración del "yo", revelando emociones, deseos y preferencias cotidianas. En este sentido, el cuidado del hermano del niño hospitalizado se define por la oferta de juego libre, para que pueda demostrar su sentimiento de seguir siendo en sus interacciones con el mundo, en el que el contexto hospitalario se ha convertido en parte de la realidad.

Abstract Objective: to understand, by means of dramatic therapeutic play, the meaning, for the sibling, of visiting the child hospitalized in intensive care. Method: a qualitative research, phenomenological modality, which used the dramatic therapeutic play to access the siblings' experiences. It was carried out in a Pediatric Intensive Care Unit in the countryside of the State of São Paulo, Brazil. Eleven siblings under ten years of age participated in the therapeutic play sessions, which were analyzed in the light of the Theory of Maturation. Results: the siblings, having a place to play, dramatized previously lived situations, from their daily life and from the visit to the hospitalized child. By living creatively, they revealed that playing is to integrate the experiences of the "I", favoring the continuity of being in the face of the situation lived. Conclusions and implications for practice: the Dramatic Therapeutic Play understood in the light of a theoretical framework allowed the sibling to mean the visit as an experience of integration of the "I", revealing emotions, desires and preferences of daily life. In this sense, the care for the brother of the hospitalized child is defined by the offer of free play, so that he demonstrates the feeling of continuing to be in his interactions with the world, in which the hospital context has become part of reality.

Perspectivas de adolescentes sobre a prática de cuidado dos irmãos: um estudo qualitativo / Perspectives of adolescents about their sibling caretaking: a qualitative study / Perspectivas de los adolescentes sobre la práctica de cuidado del hermano: un estudio cualitativo

Este estudo buscou investigar as perspectivas de adolescentes sobre a prática de cuidado dos irmãos. A amostra foi composta por seis adolescentes de ambos os sexos, com idades entre 11 e 19 anos. Os dados foram coletados por meio de entrevistas semiestruturadas e as informações foram submetidas à análise de conteúdo. Ressalta-se a importância das atividades desempenhadas pelos adolescentes no contexto familiar para o sustento financeiro da família. A percepção do cuidador sobre o cuidado dispensado aos irmãos abarcou aspectos positivos e negativos, sendo também considerada uma prática normal e rotineira. Dentre os pontos positivos, constatou-se transmitir algo de bom aos irmãos, os desafios e facilidades na realização de atividades de cuidado com os irmãos menores. A prática do cuidado pode contribuir para o sentimento de importância no contexto familiar, como também ser percebida como uma falha das mães no cumprimento de suas responsabilidades. As percepções negativas referiram-se à limitação dos tempos de lazer, à rotina estressante e à mediação de brigas entre os irmãos menores. Evidencia-se a importância de analisar o que essa prática representa para os adolescentes cuidadores, já que esta pode estar associada a sentimentos de desconforto, influenciar o bem-estar, bem como limitar a realização de atividades de lazer.(AU)

This study sought to investigate the perspectives of adolescents about their sibling caretaking. The sample consisted of six adolescents of both sexes, aged between 11 and 19 years old. The data were collected through semi-structured interviews and were submitted to content analysis. The importance of the activities performed by adolescents in the family context for the financial support of the family is emphasized. The caregiver's perception of the care given to siblings contained positive and negative aspects, and was also considered to be routine practice. Among the positives factors, it was found to transmit something good to the siblings, the challenges and facilities in carrying out care activities to younger siblings. The sibling caretaking practice can contribute to the feeling of importance in the family context, as well as being perceived as a failure of mothers in carrying out their responsibilities. Negative perceptions referred to the limitation of leisure time, the stressful routine and the mediation of fights between younger siblings. The importance of analyzing what this practice represents for young caregivers is evident, as it can be associated with uncomfortable feelings, influence well-being, as well as limit the performance of leisure activities.(AU)

Este estudio buscó investigar las perspectivas de los adolescentes sobre la práctica del cuidado de los hermanos. La muestra estuvo formada por seis adolescentes de ambos sexos, con edades comprendidas entre los 11 y los 19 años. La información se recopiló a través de entrevistas semiestructuradas y la información se sometió a análisis de contenido. Se enfatiza la importancia de las actividades que realizan los adolescentes en el contexto familiar para el apoyo financiero de la familia. La percepción del cuidador sobre el cuidado brindado a los hermanos contenía aspectos tanto positivos como negativos, y también se considera una práctica normal y rutinaria. Entre los puntos positivos, se encontró transmitir algo bueno a los hermanos, los desafíos y facilidades para realizar actividades de cuidado con los hermanos menores. La práctica del cuidado puede contribuir al sentimiento de importancia en el contexto familiar, además de ser percibida como un fracaso de las madres en el cumplimiento de sus responsabilidades. Las percepciones negativas se referían a la limitación del tiempo libre, la rutina estresante y la mediación de peleas entre hermanos menores. Es evidente la importancia de analizar lo que representa esta práctica para los cuidadores adolescentes, ya que puede asociarse a sentimientos de malestar, influir en el bienestar, así como limitar la realización de actividades de ocio.(AU)

Infección por parvovirus humano B19 en pacientes con enfermedad de células falciformes: a propósito de dos hermanos / Human parvovirus B19 infection in sickle cell disease patients: a two siblings report

Resumen La infección por parvovirus humano B19 es una de las complicaciones comunes en pacientes diagnosticados de enfermedad de células falciformes (ECF). Se caracteriza por una anemia grave con reticulocitopenia, pudiendo estar acompañada de otras manifestaciones clínicas. En ocasiones, la infección puede ocurrir de modo simultáneo en contactos intrafamiliares de un paciente también con ECF. Es fundamental el reconocimiento temprano de esta complicación y el diagnóstico diferencial con otras patologías para su correcto manejo y tratamiento. Presentamos el caso de dos hermanos con ECF e infección por parvovirus humano B19.

Abstract Human parvovirus B19 infection is one of the common complications of patients diagnosed with Sickle cell disease (SCD). Parvovirus infections are characterized by a severe anemia with reticulocytopenia, sometimes presenting with other clinical manifestations. The infection can occur simultaneously in patient's cohabitants also diagnosed with SCD. Early recognition and differential diagnosis are essential for a proper disease management and treatment. We present two siblings with SCD and human parvovirus B19 infection.

Application of ITO Method in Determination of Special Half-Sibling Relationship / 法医学杂志

OBJECTIVES@#To identify whether the relationship between Zhang A, Zhang B, Zhang C and Zhang X is the half-sibling relationship whose mother is sister (hereinafter referred to as the special half-sibling relationship) or the common first cousin relationship and discuss the application of ITO method in discriminating the special kinship.@*METHODS@#DNA was extracted from blood stain of four identified individuals, PowerPlex® 21 System and AGCU 21+1 STR kit were used to detect autosomal STR genetic markers. Investigator® Argus X-12 QS kit was used to detect the X chromosome STR genetic markers, the special half-sibling index (SHSI) and first cousin index (FCI) and their likelihood ratio (LR) were calculated by ITO method.@*RESULTS@#The LR results of SHSI to FCI, which were calculated based on autosomal STR genotyping and the analysis of X-STR genotyping results suggested that the relationship between Zhang A, Zhang B, Zhang C and Zhang X was inclined to be a special half-sibling relationship.@*CONCLUSIONS@#For the identification of special kinship, it is necessary to comprehensively apply various genetic markers according to the case. After the conclusion that shared alleles cannot be excluded from the analysis, ITO method can be further used to establish discriminant assumptions according to the specific case to obtain objective and reliable identification opinions.

Influences of family and household characteristics on children's level of physical activity during social distancing due to covid-19 in brazil / Influências das características familiares e domiciliares no nível de atividade física infantil durante o distanciamento social por covid-19 no brasil

ABSTRACT Objective: To evaluate if the variables child's sex, age, presence of siblings, parents working remotely, and external space affect the level of physical activity (PA) of Brazilian children during social distancing imposed by the COVID-19 pandemic. Methods: An online questionnaire was applied by the LimeSurvey software from March to April 2020. Children were divided into four age groups, and the questionnaire comprised questions on family and household characteristics, domestic and children's routines in the period of Brazilian social distancing. Based on the answers concerning children's activities, the following variable was created: percentage of physical activity (%PA) in one-day period. Analysis of variance and regression analysis were performed to investigate the effect of demographic and parental activities on %PA. Results: The %PA decreases with increasing age, but increases with the availability of external space at home. No significant or interaction effects were observed for other variables. Age and external space at home are predictors of %PA. Conclusions: Household and personal characteristics of Brazilian children influence the level of physical activity performed by them during social distancing. Preventive measures can be adopted in the face of another similar period.

RESUMO Objetivo: Investigar se as variáveis sexo da criança, idade, presença de irmãos, pais trabalhando de maneira remota e espaço externo afetam o nível de atividade física das crianças brasileiras durante o distanciamento social por COVID-19. Métodos: Aplicou-se questionário online pelo LimeSurvey, em março e abril de 2020, sobre características familiares e habitacionais, rotinas domésticas e infantis no período de distanciamento social brasileiro, sendo as crianças divididas em quatro grupos etários. Com base nas atividades infantis realizadas, criou-se a porcentagem de atividade física (%AF) em relação ao período de um dia e foi desenvolvida análise de variância para investigar o efeito das variáveis na %AF, além de análise de regressão. Resultados: A %AF diminui conforme o aumento da idade, mas aumenta com a disponibilidade de espaço externo no domicílio. Não houve efeito significativo para as demais variáveis, tampouco efeito de interação. A idade e o espaço externo ao domicílio são preditores da %AF. Conclusões: Características habitacionais e pessoais das crianças brasileiras influenciam o nível de atividade física realizada por elas durante o distanciamento social. Medidas preventivas podem ser empregadas caso haja necessidade de outro período semelhante.

Glycogen storage syndrome type 0 caused by GYS2 gene variation and phenotypic differences between two siblings / 中华医学遗传学杂志

OBJECTIVE@#To provide a basis for genetic counseling and clinical precision therapy by exploring the genetic etiology of a child with recurrent hypoglycemia convulsion accompanied by language retardation.@*METHODS@#Peripheral blood samples were obtained from the proband, his sister and his parents. Whole genomic DNA was extracted and analyzed by the whole exon gene sequencing and confirmed by Sanger sequencing.@*RESULTS@#The proband and his sister were found to carry compound heterozygous variants c.731T>A (p.M244L) and c.928G>A (p.G244S) of the GYS2 gene, which had not been reported in the past, the c.731T>A (p.M244L) site was derived from the maternal heterozygous mutation, while c.928G>A (p.G244S) site from the father heterozygous mutation.@*CONCLUSION@#The compound heterozygous variants c.731T>A (p.M244L) and c.928G>A (p.G244S) of the GYS2 gene were the genetic cause of glycogen storage syndrome type 0 in children, providing basis for family genetic counseling. When the patient had Hypoglycemia often accompanied with convulsions, which was easy to be misdiagnosed as seizures, and the antiepileptic treatment was ineffective. After genetic diagnosis, the seizure can be controlled by improving diet to maintain blood glucose stability.

Autism spectrum disorder/development delay in siblings with SCN2A mutations caused by germline mosaicism / 中华医学遗传学杂志

OBJECTIVE@#To report on a family which has two siblings with SCN2A mutation caused by germline mosaicism suffering from autism spectrum disorder/development delay (ASD/DD).@*METHODS@#Clinical data was collected for the proband and his parents. Next generation sequencing (NGS) was carried out on the proband and his parents. Suspected mutations were verified by Sanger sequencing of the proband, his parents and brother. To detect whether there is a low proportion of somatic mosaicism in the parents, a droplet digital PCR was conducted. The result of ddPCR showed that the father was germline mosaicism (0.233%).@*RESULTS@#NGS has identified a de novo splicing mutation of the SCN2A gene, c.605+1G>A, in the proband and his brother. Combined with its clinical phenotype and inheritance pattern, SCN2A was judged to be the pathogenic gene. Above findings strongly suggested parental germline mosaicism.@*CONCLUSION@#ASD/DD in siblings with SCN2A mutations caused by germline mosaicism. Paternal mosaicism should be considered as one of the important inheritance patterns for counseling parents with a child carrying SCN2A mutation. The ddPCR can help to reveal very low proportion of germline mosaicism.

Siblings Seckel's syndrome 1 caused by ATR gene variants in a sibpair / 中华医学遗传学杂志

OBJECTIVE@#Two brothes with Seckel's syndrome 1(SCKL1) were reported and a literature review was carried to provide clinical and genetic information of this rare disease.@*METHODS@#Clinical data of the two children were collected, and the peripheral blood was extracted for whole exome sequencing. Literature of the disease were reviewed.@*RESULTS@#The two patients were 11 years and 9.5 years old when examined for short stature. They presented with intrauterine growth retardation, intellectual disability, microcephaly, birdhead-like face and coffee au lait spots. The bone age was more than 2 years behind the chronical age and the growth hormone levels were normal. Whole exome sequencing revealed novel compound heterozygous variants c.1A>G (p.M1?) and c.4853-18A>G of ART gene in both children.@*CONCLUSION@#Children with prenatal onset short stature, developmental delay, microcephaly and special facial featuresshould be considered for the possibility of Seckel's syndrome, whole exome sequencing could help to confirm the clinical diagnosis.

The being who being-in-the-world … becomes mother of a second child / El ser que siendo-en-el-mundo … Se convierte en madre de un segundo hijo / O ser que sendo-no-mundo … se torna mãe de um segundo filho

ABSTRACT Becoming mother of a second child, as a parental transition phenomenon, poses a challenge to reflection in Nursing. This theoretical study intends to present a reflection on the being who being-in-the-world becomes mother of a second child. It is based on Heideggerian phenomenology and nursing thought. The text is organized around two axes: Heidegger's conceptual contributions and nursing thought. The Heideggerian ontological dimension, aligned with the humanistic presuppositions of Nursing, contributes to unfold the meanings of life experiences and broaden possibilities of caring of the being who being-in-the-world… becomes mother of a second child. Concomitantly, the access to the experience of women who being-in-the-world become mother of a second child enables widening comprehension of this phenomenon, which will certainly impact nurses' being-present in their daily care.

RESUMEN Convertirse en madre de un segundo hijo, en tanto que fenómeno de transición a la parentalidad, se configura como un desafío a la reflexión de Enfermería. Este estudio teórico pretende presentar una reflexión sobre el ser que, siendo-en-el-mundo, se convierte en madre de un segundo hijo a la luz de la fenomenología heideggeriana y del pensamiento enfermero. El texto se organizó en torno a dos ejes: las contribuciones conceptuales de Heidegger y el pensamiento enfermero. Se identifica que la dimensión ontológica heideggeriana, junto con los presupuestos humanísticos de la Enfermería, contribuyen a desvelar los sentidos de lo vivido y a ampliar las posibilidades de cuidar al ser que, siendo-en-el-mundo… se convierte en madre de un segundo hijo. Concomitantemente, el acceso a la experiencia de la mujer que, siendo-en-el-mundo, se convierte en madre de un segundo hijo, permite abrir el horizonte de comprensión del fenómeno, lo que sin duda repercutirá en el modo de ser-presente de los enfermeros en sus cuidados diarios.

RESUMO Tornar-se mãe de um segundo filho, enquanto fenómeno de transição na parentalidade, configura-se como um desafio à reflexão em Enfermagem. Pretende-se neste estudo teórico apresentar uma reflexão sobre o ser que sendo-no-mundo se torna mãe de um segundo filho à luz da fenomenologia heideggeriana e do pensamento de enfermagem. O texto foi organizado em torno de dois eixos: os contributos conceptuais de Heidegger e o pensamento de enfermagem. Identifica-se que a dimensão ontológica heideggeriana, alinhada com os pressupostos humanísticos da Enfermagem, contribui para desvelar os sentidos do vivido e ampliar as possibilidades de cuidar do ser que sendo-no-mundo… se torna mãe de um segundo filho. Concomitantemente, o acesso à experiência da mulher que sendo-no-mundo se torna mãe de um segundo filho permite abrir o horizonte de compreensão face ao fenómeno, o que certamente terá impacto no modo de ser-presente do enfermeiro no quotidiano de cuidados.