Clinical phenotype and genetic analysis of a fetus with Cardiac valvular dysplasia type 1 / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with Cardiac valvular dysplasia type 1 (CVDP1).@*METHODS@#A CVDP1 fetus identified at the Ningbo Women and Children's Hospital on July 7, 2022 was selected as the study subject. Clinical data of the fetus was collected. The fetus and its parents were subjected to trio-whole exome sequencing (trio-WES), and candidate variants were verified by Sanger sequencing.@*RESULTS@#The fetus had exhibited generalized edema, complex cardiac malformation, abdominal effusion, and enhanced intestinal and renal parenchymal echoes. Trio-WES revealed that it has harbored compound heterozygous variants of the PLD1 gene, namely c.2977C>T (p.R993*) and c.1460G>A (p.W487*), which were respectively inherited from its father and mother. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2977C>T (p.R993*) variant was evaluated to be likely pathogenic (PVS1_Moderate+PM2_Supporting+PM3+PP4), whilst the c.1460G>A (p.W487*) variant was evaluated to be pathogenic (PVS1+PM2_Supporting+PP4).@*CONCLUSION@#The c.2977C>T (p.R993*) and c.1460G>A (p.W487*) compound heterozygous variants of the PLD1 gene probably underlay the CVDP1 in the fetus. Above discovery has enriched the mutational spectrum of the PLD1 gene and provided a guidance for genetic counseling and prenatal diagnosis in this family.

Clinical characteristics and genetic counseling for a three-generation Chinese pedigree with recurrent fetal Kabuki syndrome due to variant of KDM6A gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a pregnant woman with a history of adverse pregnancy outcomes.@*METHODS@#A woman with an adverse history of pregnancies including one fetal demise and two induced abortions due to fetal diaphragmatic hernia and complex cardiac anomalies was selected as the study subject. Muscle tissue from the induced abortus was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing of the couple and other family members.@*RESULTS@#Genetic sequencing revealed that the fetus has harbored a frameshift variant of the KDM6A gene (NM_001291415.2), namely c.1228_1229del (p.Gln410GlufsTer2), which was inherited from the woman and her mother. The variant was unreported previously, and the woman was found to have short stature, sparse eyebrows in the outer third, peculiar facial features, but normal intelligence in addition with female congenital genital malformation, like incomplete vaginal septum, double cervix, double uterus, and unilateral ovary absence. mostly similar phenotypes observed in her mother.@*CONCLUSION@#The hemizygous c.1228_1229del variant of the KDM6A gene probably underlay the abnormalities in the fetus. All findings have enabled genetic counseling for this family featuring X-linked inheritance, and the woman had given birth to a healthy girl with appropriate prevention and intervention.

Resultado a largo plazo de una serie de fetos con agenesia aislada del septum pellucidum / Long-term postnatal outcome of fetuses with isolated agenesis of the septum pellucidum

Objetivo: Reportar el resultado a largo plazo de una serie de fetos con agenesia del septum pellucidum aislada (ASP), con medición de su quiasma óptico mediante neurosonografía fetal (NSG). Método: Se incluyeron todas las pacientes con ASP y NSG evaluadas desde el año 2008 a la fecha y con seguimiento hasta su edad escolar. En todos los casos se consignaron los datos clínicos de NSG y de resonancia magnética (RM), cuando esta se realizó. Se entrevistó telefónicamente a los padres. Resultados: Nueve pacientes cumplieron los criterios: cuatro con displasia septo-óptica (DSO) (rango de seguimiento: 5-14 años) y cinco sin DSO (rango de seguimiento: 7-10 años). Un décimo caso se excluyó por tener solo 6 meses de seguimiento. Ninguna de las ASP tuvo otra anomalía detectada en su seguimiento. Ninguno de los casos con DSO tuvo alteración del tamaño de su quiasma óptico en la NSG ni anormalidad en la vía óptica en la RM. Conclusiones: En nuestra población, el riesgo residual de DSO frente a ASP es del 44,4%. En el seguimiento, nuestra definición de ASP por NSG no tuvo falsos negativos con relación a otras anomalías de aparición posnatal, a excepción de la DSO.

Objective: To report the long-term outcome of a series of fetuses with isolated septum pellucidum agenesis (ASP) with measurement of their optic chiasm by fetal neurosonography (NSG). Method: All patients with ASP and NSG evaluated from 2008 to date and with follow-up until their school age were included. In all cases, clinical, NSG and magnetic resonance imaging (MRI) data were recorded. Parents were interviewed by telephone. Results: Nine patients met the criteria: four with septo-optic dysplasia (SOD) (follow-up range: 5-14 years) and five without SOD (follow-up range: 7-10 years). A tenth case was excluded because only 6 months of follow-up. None of the ASP cases had another anomaly detected in their follow-up. None of the cases with DSO had anomaly of the size of their optic chiasm on NSG or abnormality in the optical pathway in the MRI. Conclusions: In our population, the residual risk of DSO versus ASP is 44.4%. At follow-up, our NSG definition of ASP had no false negatives in relation to other postnatal-onset anomalies, except for SOD.

É preciso um pacto para erradicar a sífilis congênita no Estado do Rio de Janeiro / A pact is needed to eradicate congenital syphilis in the State of Rio de Janeiro

Os números mostram que os municípios do Rio de Janeiro não têm conseguido diagnosticar precisamente ou tratado adequadamente suas gestantes, resultando na infecção e mortes de bebês. A transmissão vertical é de 70 a 100% dos casos, com morte de 40% doas fetos. A sífilis congênita é a mais antiga infecção congênita e a primeira pandemia com tratamento disponível no SUS, mas persiste por falta de diagnóstico e tratamento oportuno. Os casos de sífilis congênita atesta que falta qualidade às consultas. É preciso implementar esse pacto de ações na comissão Intergestores Bipartite do Rio de Janeiro: cabe à Secretaria de Estado articular com os secretários municipais o delineamento da política pública e sua implementação. (AU)

Revisión Exploratoria: Comunicación de la Articulación Temporomandibular y del Oído Medio en Fetos y Niños / Exploratory Review: Temporomandibular Joint and Middle Ear Communication in Fetuses and Infants

La Articulación temporomandibular (ATM) cumple funciones importantes para la vida; su adecuado funcionamiento se puede alterar por trastornos temporomandibulares (TTM). La sintomatología de los TTM es variada, entre ellos se encuentra dolor en los músculos masticatorios, ruidos articulares y con menos frecuencia algunos pacientes refieren síntomas auditivos, lo que sugiere la existencia de una relación entre la ATM y el oído medio; sin embargo, esta relación no es clara. En consecuencia, el presente estudio tiene como propósito realizar una revisión de literatura para identificar los aspectos conocidos, desconocidos y controvertidos sobre la relación entre la ATM y el oído medio en niños y fetos. Se efectuó una búsqueda de la literatura en bases de datos utilizando los operadores booleanos (AND/OR) y los términos clave en inglés y en español. Se identificaron inicialmente 1080 artículos, se eliminaron los artículos duplicados y se aplicaron los criterios de inclusión y exclusión. Finalmente, se seleccionaron un total de 14 artículos que se revisaron a texto completo. Los estudios encontrados se enfocan en el desarrollo histoembriológico de la ATM y cómo ese desarrollo se da en conjunto con los componentes del oído medio. Adicionalmente, se identificaron investigaciones sobre el origen, la morfología y función del ligamento discomaleolar, el ligamento esfenomandibular y la fisura petrotimpánica como estructuras que conectan la ATM y el oído medio, pero los resultados han sido controvertidos. Se concluye que son necesarios más estudios para determinar cualquier relación anatómica y fisiológica que pueda existir entre la ATM y el sistema auditivo en fetos y niños.

SUMMARY: The temporomandibular joint (TMJ) has important functions for life; its proper functioning can be altered by temporomandibular disorders (TMD). The symptomatology of TMD is varied, including pain in the masticatory muscles, joint noises and less frequently some patients report auditory symptoms, suggesting the existence of a relationship between the TMJ and the middle ear; however, this relationship is not clear. Consequently, the present study aims to conduct a literature review to identify the known, unknown and controversial aspects of the relationship between TMJ and the middle ear in children and fetuses. A literature search was performed in databases using Boolean operators (AND/ OR) and key terms in English and Spanish. A total of 1080 articles were initially identified; duplicate articles were eliminated and inclusion and exclusion criteria were applied. Finally, a total of 14 articles were selected and reviewed in full text. The studies found focus on the histoembryological development of the TMJ and how that development occurs in conjunction with the middle ear components. Additionally, research on the origin, morphology, and function of the discomalleolar ligament, sphenomandibular ligament, and petrotympanic fissure as structures connecting the TMJ and middle ear was identified, but the results have been controversial. It is concluded that further studies are necessary to determine any anatomical and physiological relationship that may exist between the TMJ and the auditory system in fetuses and children.

Dissecação anatômica como estratégia para o estudo do sistema neural em fetos humanos / Anatomic dissection as a strategy for the study of the neural system in fetuses / Disección anatómica como estrategia para el estudio del sistema neural en fetos

Esse trabalho busca relatar o processo de confecção de peças anatômicas para o ensino da anatomia humana a partir de material cadavérico fetal. Os discentes do curso de medicina da Universidade Federal do Paraná (UFPR) ­ Campus Toledo participaram do programa de voluntariado acadêmico e deram atenção especial aos aspectos técnicos do processo de dissecação, bem como a experiência subjetiva desse procedimento como ferramenta de aprendizado ativo. O procedimento foi realizado na sala de preparação de cadáver da UFPR ­ Campus Toledo, utilizando instrumental de dissecação e cadáveres humanos fetais com 20, 17 e 14 semanas de idade gestacional, direcionado de modo a expor as partes constituintes do sistema neural. Foram confeccionadas peças de cérebro, cerebelo, tronco encefálico, medula espinal, nervos espinais e suas estruturas associadas. Os voluntários envolvidos foram capazes de produzir material de estudo de qualidade através da dissecação e fortalecer seu conhecimento em anatomia humana e aptidão manual. Também foi dada atenção à importância e às limitações do processo de dissecação como estratégia de aprendizado em cursos da área de saúde. pôde ser observado que a dissecação pode fazer parte de uma formação completa e bem estruturada dos discentes, que por sua vez irão integrar a sociedade e a academia. Além disso, a exposição da topografia neural fetal pode servir de referencial para posteriores estudos que venham a utilizar essas informações.

This work aims to report the confection process of anatomic pieces for teaching human anatomy from fetal cadaveric material. The students of the medicine course of Universidade Federal do Paraná (UFPR) ­ Campus Toledo, took part in the academic volunteer program and paid special attention to the technical aspects of the dissection process, as well as the subjective experience of this procedure as an active learning tool. The procedure was performed at the cadaver preparation room of the UFPR ­ Campus Toledo, using dissection tools and human fetal corpses of 20, 17 and 14 weeks of gestational ages, directed so as to expose the constituent parts of the neural system. Pieces of the brain, cerebellum, brainstem, spinal cord, spinal nerves, and its associated structures were made. The involved voluntaries were able to produce quality study material through dissection, and strengthen their knowledge in human anatomy and manual skill. Attention was also given to the importance and limitations of the dissection process as a learning strategy in health courses. it was observed that dissection can be part of a complete and well-structured training of students, who in turn will integrate society and academia. In addition, the exposure of fetal neural topography can serve as a reference for further studies that use this information

Este trabajo tiene como objetivo relatar el proceso de confección de piezas anatómicas para la enseñanza de la anatomía humana a partir de material cadavérico fetal. Los alumnos del curso de medicina de la Universidade Federal do Paraná (UFPR) - Campus Toledo, participaron del programa de voluntariado académico y prestaron especial atención a los aspectos técnicos del proceso de disección, así como a la vivencia subjetiva de este procedimiento como herramienta de aprendizaje activo. El procedimiento fue realizado en la sala de preparación de cadáveres de la UFPR - Campus Toledo, utilizando herramientas de disección y cadáveres de fetos humanos de 20, 17 y 14 semanas de edad gestacional, dirigidos de forma a exponer las partes constitutivas del sistema neural. Se realizaron piezas del cerebro, cerebelo, tronco encefálico, médula espinal, nervios espinales y sus estructuras asociadas. Los voluntarios participantes pudieron elaborar material de estudio de calidad mediante la disección y reforzar sus conocimientos de anatomía humana y habilidad manual. También se prestó atención a la importancia y las limitaciones del proceso de disección como estrategia de aprendizaje en los cursos de salud. Se observó que la disección puede formar parte de una formación completa y bien estructurada de los estudiantes, que a su vez integrarán la sociedad y el mundo académico. Además, la exposición de la topografía neural fetal puede servir de referencia para estudios posteriores que utilicen esta información.

Índice de massa corpórea de recém-nascidos de gestações de baixo risco segundo idade gestacional e sexo / Newborns' body mass index from low-risk pregnancies according to gestational age and sex

O estado nutricional e o crescimento alcançado pelo recém-nascido tem sido utilizados como marcador/indicador de riscos de morbimortalidade precoce e até de problemas em idades mais avançadas. Como consequência o Indice de Massa Corpórea (IMC) pode ser instrumento útil para esta finalidade. O objetivo foi analisar o IMC de recém-nascidos de 34 a 41 semanas completas de idade gestacional (IG) de gestações de baixo risco. Trata-se de um estudo descritivo, analítico e quantitativo, desenvolvido a partir do banco de dados do projeto "Características biométricas ao nascimento, de filhos de mulheres adultas jovens, em um município de elevado índice de desenvolvimento humano". Foram incluídos no estudo todos os RN nascidos vivos no período de maio de 2015 e março de 2018 no Hospital Universitário de Taubaté, filhos de mulheres sem morbidade, que apresentavam em seus registros: a data do parto, idade e/ou data de nascimento materna, tipo de gestação, tipo de parto, IG, sexo, peso, comprimento e perímetro craniano ao nascimento. Foram excluídos os recém-nascidos de gestações gemelares, portadores de malformações ou outras morbidades. Também foram excluídos os que apresentavam valores extremos, acima de 3 desvios padrão em relação à média ou dados inconsistentes no arquivo. Realizaram-se análises de tendência central e dispersão dos valores, além das correlações entre IG e o peso do RN, e o comprimento do RN, e análise da correlação entre IG e o IMC do RN, sempre por sexo. Além disso, foram feitas comparações entre a evolução dos valores estimados de IMC por IG e sexo e os valores publicados por Olsen et.al (2015), Brock et.al (2008) e Davidson et.al (2011) e das tendências de evolução do IMC segundo a classificação ao nascimento em: pequenos para a idade gestacional (PIG), adequados para a IG (AIG) e grandes para a IG (GIG). Dos 6.321 nascidos no período, 6.138 preencheram os critérios de inclusão, destes 3.074 (50,1%) eram do sexo masculino. Metade da população de estudo nasceu entre 38 e 40 semanas de IG, com peso AIG, comprimento entre 46,5cm e 49 cm. A prevalência de partos vaginais foi de 60,1%. A descrição dos valores de IMC, mostrou um crescimento compatível com a evolução da idade gestacional tanto para recém-nascidos do sexo masculino quanto feminino. O comportamento do IMC ao nascimento, tanto em valor absoluto quando em escore-z, mostrou diferenças entre os três grupos de classificação da adequação dos RN, com os maiores valores observados entre os GIG e os menores para os PIG, tanto em meninos quanto em meninas, segundo IG. A tendência de evolução de acordo com a IG dos valores estimados de IMC foi semelhante com a tendência dos outros autores, embora em patamares de valores absolutos distintos. A interpretação destes resultados aponta a necessidade de se desenvolver novas pesquisas para estudar o comportamento do IMC, particularmente no Brasil, para verificar se resultados do IMC semelhantes são observados também em outras cidades/Estados/regiões e confirmar o possível papel do crescimento em comprimento na produção de valores de IMC aparentemente favoráveis. Além disso é também de interesse verificar uma possível influência intergeracional nos valores de crescimento do comprimento intraútero, no nosso meio.

The nutritional status and growth of the newborn (NB) have been used as a marker/indicator of morbidity and mortality risks that may occur at more advanced ages. This study aimed to analyze NBs' body mass index (BMI) born between 33 and 41 completed weeks of gestational age (GA) of low-risk pregnancies. This descriptive, analytical, quantitative, and retrospective study was developed from the project's database "Biometric characteristics at birth, of children of young adult women, in a municipality with a high human development index". All NBs born alive from single pregnancies from adult women and were born between May 2015 and March 2018 at the University Hospital of Taubaté, who presented in their records at least the date of delivery, maternal age and/or maternal date of birth, type of pregnancy, type of delivery, gestational age (GA), sex, weight at birth, and length at birth were included in the study. Analysis of the correlation between GA and NB weight by sex was carried out by calculating the correlation coefficient and its respective significance. As well as the correlation between GA and NB length by sex and analysis of the correlation between GA and BMI of the NB by sex. Additionally, graphic comparisons were made with the evolution of BMI by GI and sex and the values published by researchers Olsen et al. (2015), Brock et al. (2008), and Davidson et al. (2011) and BMI evolution trends according to the classification at birth in small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). In the study period, 6.321 children were born, and 6,138 met the inclusion criteria, being 3,074 males and 3.064 females. Half of the study population was born between 38 and 40 weeks of gestation, with AGA birth weight, a length between 46.5cm and 49 cm, and a prevalence of 60.1% of vaginal deliveries. The description of BMI values showed growth compatible with the evolution of GA for both male and female NBs. The behavior of BMI at birth, both in absolute value and in z-scores, showed that there was a difference between the three groups for classifying the adequacy of NBs proposed by Battaglia and Lubchenco (1967), with the highest values observed among the LGA and the smallest for SGA, both for boys and girls at different GAs. The interpretation of these results also opens some perspectives for the development of new research, particularly in Brazil, to verify whether similar BMI results are also observed in other cities/states/regions, in addition to demonstrating a possible intergenerational influence and confirming the potential role of growth in length in producing favorable BMI values.

Fisiología respiratoria: el pulmón al momento de nacer / Respiratory Physiology - the lung at the moment of birth

La adaptación fisiológica de los recién nacidos de la vida intrauterina a la extrauterina incluye cambios fisiológicos complejos. Para que se complete con éxito la transición fetal a neonatal, los recién nacidos deben lograr el aclaramiento de líquido pulmonar, la generación de CRF e inicio de la respiración, para permitir el intercambio de gases y la oxigenación de los tejidos. En este artículo se describen estos mecanismos, algunas bases del desarrollo pulmonar y de la circulación fetal; y las medidas que se requieren para asistir al recién nacido cuando no logran completar esta transición espontáneamente, lo que ocurre en el 5 al 10 % de los casos.

The physiological adaptation of newborns from intrauterine to extrauterine life includes complex physiological changes. For the fetal to neonatal transition to be successfully completed, neonates must achieve lung fluid clearance, FRC generation, and initiation of respiration to allow gas exchange and tissue oxygenation. This article describes these mechanisms, some bases of lung development and fetal circulation; and the measures required to assist the newborn, when they fail to complete this transition spontaneously, which occurs in the 5 to 10% of cases.

Saúde mental e abortamento voluntário na audiência pública da ADPF442/STF / Mental health and voluntary abortion in the public hearing of ADPF442/STF / Salud mental y aborto voluntario en la audiencia pública del ADPF442/STF

O estudo teve como objetivo identificar os argumentos da estratégia de persuasão dos discursos apresentados na audiência pública sobre a Arguição de Descumprimento de Preceito Fundamental-ADPF 442, realizada em 2018, cujo propósito era discutir sobre a interrupção voluntária da gravidez até a 12ª semana. Para tal, foi realizada uma pesquisa de abordagem qualitativa, analítico-descritiva e documental. O objeto de análise foi o registro da audiência, apresentado em vídeo, disponibilizado na plataforma digital YouTube, e em ata lavrada pelo STF, ambos de acesso público. A partir de uma análise do discurso, identificou-se os argumentos utilizados na estratégia de persuasão, que foram sistematizados em quatro categorias de argumentos para cada um dos dois grupos identificados: o grupo pró e o grupo contra a descriminalização do aborto. As três primeiras categorias, Saúde mental, Direito e Saúde pública, mesmo com diferenças na forma de apresentar o argumento, se repetem nos dois grupos. Todavia, a quarta categoria, Pressupostos, se diferenciou. No grupo pró descriminalização do aborto, apresentou-se como Pressupostos filosóficos e científicos, e no grupo contra, como Pressupostos morais. Por fim, a defesa da saúde mental das mulheres foi o principal argumento numa forma de humanizar o sofrimento vivido pelas que desejam abortar e não encontram o suporte do Estado para assegurar sua dignidade, cidadania e efetiva igualdade, garantidas constitucionalmente.(AU)

The study aimed to identify the arguments of the persuasion strategy of the speeches presented at the public hearing on the Action Against the Violation of Constitutional Fundamental Rights -ADPF 442, held in 2018, whose purpose was to discuss the voluntary interruption of pregnancy until the 12th week. To this end, a qualitative, analytical-descriptive, and documentary research was carried out. The object of analysis was the video recording of the hearing available on the YouTube platform, and in minutes drawn up by the STF, both of which are public. Based on a discourse analysis, the arguments used in the persuasion strategy were identified, which were systematized into four categories of arguments for each of the two identified groups: the group for and the group against the decriminalization of abortion. The first three categories, Mental Health, Law and Public Health, even with differences in the way of presenting the argument, are repeated in both groups. However, the fourth category, Assumptions, differed. In the group for the decriminalization of abortion, it was presented as Philosophical and Scientific Assumptions, whereas the group against, as Moral Assumptions. Finally, the defense of women's mental health was the main argument in a way of humanizing the suffering experienced by those who wish to have an abortion and do not find the support of the State to guarantee their dignity, citizenship, and effective equality, constitutionally guaranteed.(AU)

El estudio tuvo como objetivo identificar los argumentos de la estrategia de persuasión de los discursos presentados en la audiencia pública sobre el Argumento por Incumplimiento de un Percepto Fundamental -ADPF 442, realizada en 2018, con el objetivo de discutir la interrupción voluntaria del embarazo hasta la 12.ª semana. Para ello, se llevó a cabo una investigación cualitativa, analítico-descriptiva y documental. El objeto de análisis fue la grabación de la audiencia, que está disponible en la plataforma digital YouTube, y actas levantadas por el Supremo Tribunal Federal -STF, ambas de acceso público. A partir de un análisis del discurso se identificaron los argumentos utilizados en la estrategia de persuasión, los cuales se sistematizaron en cuatro categorías de argumentos para cada uno de los dos grupos identificados: el grupo pro y el grupo en contra de la despenalización del aborto. Las tres primeras categorías ("salud mental", "derecho" y "salud pública") aún con diferencias en la forma de presentar el argumento se repiten en ambos grupos. Pero difiere la cuarta categoría "supuestos". En el grupo a favor de la despenalización del aborto se presentó como "supuestos filosóficos y científicos", y en el grupo en contra, como "supuestos morales". Finalmente, la defensa de la salud mental de las mujeres fue el principal argumento en un intento por humanizar el sufrimiento que viven aquellas que desean abortar y no encuentran el apoyo del Estado para garantizar su dignidad, ciudadanía e igualdad efectiva, preconizadas por la Constitución.(AU)

Clinical characteristics and genetic analysis of a fetus with Melnick-Needles syndrome due to variant of FLNA gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a fetus with Melnick-Needles syndrome (MNS).@*METHODS@#A fetus with MNS diagnosed at Ningbo Women and Children's Hospital in November 2020 was selected as the study subject. Clinical data was collected. Pathogenic variant was screened by using trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing.@*RESULTS@#Prenatal ultrasonography of the fetus had shown multiple anomalies including intrauterine growth retardation, bilateral femur curvature, omphalocele, single umbilical artery, and oligohydramnios. Trio-WES revealed that the fetus has harbored hemizygous c.3562G>A (p.A1188T) missense variant of the FLNA gene. Sanger sequencing confirmed that the variant was maternally derived, whilst its father was of a wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+PM2_Supporting+PP3+PP4).@*CONCLUSION@#The hemizygous c.3562G>A (p.A1188T) variant of the FLNA gene probably underlay the structural abnormalities in this fetus. Genetic testing can facilitate accurate diagnosis of MNS and provide a basis for genetic counseling for this family.

Prenatal diagnosis for a fetus with Walker-Warburg syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology for a fetus with Walker-Warburg syndrome(WWS).@*METHODS@#A fetus with WWS diagnosed at Gansu Provincial Maternity and Child Health Care Hospital in June 9, 2021 was selected as the study subject. Genomic DNA was extracted from amniotic fluid sample of the fetus and peripheral blood samples from its parents. Trio-Whole exome sequencing (trio-WES) was carried out. Candidate variants were verified by Sanger sequencing.@*RESULTS@#The fetus was found to harbor compound heterozygous variants of the POMT2 gene, namely c.471delC (p.F158Lfs*42) and c.1975C>T (p.R659W), which were respectively inherited from its father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively rated as pathogenic (PVS1+PM2_Supporting+PP4) and likely pathogenic (PM2_Supporting+PM3+PP3_Moderate+PP4).@*CONCLUSION@#Trio-WES may be used for the prenatal diagnosis of WWS. The compound heterozygous variants of the POMT2 gene probably underlay the disorder in this fetus. Above finding has expanded the mutational spectrum of the POMT2 gene and enabled definite diagnosis and genetic counseling for the family.

Analysis of clinical phenotype and pathogenic variant of a fetus with Cornelia de Lange syndrome type II / 中华医学遗传学杂志

OBJECTIVE@#To explore the prenatal ultrasonographic features and genetic basis for an abortus suspected for type II Cornelia de Lange syndrome (CdLS2).@*METHODS@#A fetus diagnosed with CdLS2 at the Shengjing Hospital Affiliated to China Medical University on September 3, 2019 was selected as the study subject. Clinical data of the fetus and family history was collected. Following induced labor, whole exome sequencing was carried out on the abortus. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#Prenatal ultrasonography (33 weeks of pregnancy) has revealed multiple anomalies in the fetus, which included slightly widened cavity of septum pellucidum, blurred corpus callosum, slightly reduced frontal lobe volume, thin cortex, fusion of lateral ventricles, polyhydramnios, small stomach bubble, and digestive tract atresia. Whole exome sequencing has revealed a heterozygous c.2076delA (p.Lys692Asnfs*27) frameshifting variant in the SMC1A gene, which was found in neither parent and was rated as pathogenic based on the guidelines of American College of Medical Genetics and Genomics (ACMG).@*CONCLUSION@#The CdLS2 in this fetus may be attributed to the c.2076delA variant of the SMC1A gene. Above finding has provided a basis for genetic counseling and assessment of reproductive risk for this family.

Analysis of MYRF gene variant in a fetus with Cardiac-urogenital syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with Cardiac-urogenital syndrome (CUGS).@*METHODS@#A fetus with congenital heart disease identified at the Maternal Fetal Medical Center for Fetal Heart Disease, Beijing Anzhen Hospital Affiliated to Capital Medical University in January 2019 was selected as the study subject. Clinical data of the fetus was collected. Copy number variation sequencing (CNV-seq) and trio-whole exome sequencing (trio-WES) were carried out for the fetus and its parents. Candidate variants were verified by Sanger sequencing.@*RESULTS@#Detailed fetal echocardiographic examination had revealed hypoplastic aortic arch. The results of trio-WES revealed that the fetus has harbored a de novo splice variant of the MYRF gene (c.1792-2A>C), for which both parents were of the wild-type. Sanger sequencing confirmed the variant to be de novo. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic. CNV-seq has identified no chromosomal anomalies. And the fetus was diagnosed with Cardiac-urogenital syndrome.@*CONCLUSION@#The de novo splice variant of the MYRF gene probably underlay the abnormal phenotype in the fetus. Above finding has enriched the spectrum of MYRF gene variants.

Clinical analysis of monochorionic-diamniotic twins with genetic discordance / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of 5 cases of monochorionic-diamniotic (MCDA) with genetic discordance.@*METHODS@#148 cases of MCDA twins who were diagnosed by amniocentesis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region from January 2016 to June 2020 were selected as the study subjects. Relevant clinical data of the pregnant women were collected, and amniotic fluid samples of the twins were collected separately. Chromosomal karyotyping analysis and single nucleotide polymorphism array (SNP array) assay were carried out.@*RESULTS@#The results of chromosomal karyotyping analysis showed that 5 of the MCDA twins had inconsistent chromosome karyotypes, with an incidence of 3.4% (5/148). SNP array assay showed that 3 fetuses were mosaics.@*CONCLUSION@#Genetic discordance occurs among MCDA twins, and prenatal counseling for such cases should be given by doctors with experience in medical genetics and fetal medicine, and personalized clinical management should be recommended.

Comparison of results of prenatal diagnosis by different techniques for fetuses with increased nuchal translucency / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of chromosomal microarray analysis (CMA) and trio-whole exome sequencing (trio-WES) for fetuses with increased nuchal translucency (NT) thickness.@*METHODS@#Sixty two pregnant women who had visited Urumqi Maternal and Child Care Health Hospital between June 2018 and June 2020 for NT ≥ 3.0 mm at 11 ~ 13+6 gestational weeks were selected as study subjects. Relevant clinical data were collected. The patients were divided into 3.0 ~ ＜3.5 mm (n = 33) and ≥3.5 mm groups (n = 29). Chromosome karyotyping analysis and chromosomal microarray analysis were carried out. And trio-WES analysis was performed on 15 samples with NT thickening but negative CMA results. The distribution and incidence of chromosomal abnormalities in the two groups were compared by using chi-square test.@*RESULTS@#The median age of the pregnant women was 29 years old (22 ~ 41 years old), the median thickness of NT was 3.4 mm (3.0 ~ 9.1 mm), and the median gestational age at the detection was 13+4 weeks (11+5 ~ 13+6 weeks). Chromosome karyotyping analysis has detected 12 cases of aneuploidies and 1 case of derivative chromosome. The detection rate was 20.97% (13/62). CMA has detected 12 cases of aneuploidies, 1 case of pathogenic CNV and 5 cases of variant of uncertain significance (VUS), with a detection rate of 29.03% (18/62). The aneuploidy rate for the NT ≥ 3.5 mm group was higher than that for the 3.0 ≤ NT < 3.5 mm group [3.03% (1/33) vs. 41.38% (12/29), χ² = 13.698, P < 0.001]. There was no statistically significant difference between the two groups in the detection rate of fetal pathogenic CNV and VUS (χ² = 0.028, P > 0.05). Trio-WES analysis of 15 samples with negative CMA result and no structural abnormality has identified 6 heterozygous variants, including SOS1: c.3542C>T (p.A1181V) and c.3817C>G (p.L1273V), COL2A1: c.436C>T (p.P146S) and c.3700G>A (p.D1234N), LZTR1: c.1496T>C (p.V499A), and BRAF: c.64G>A (p.D22N), respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were rated as VUS.@*CONCLUSION@#NT thickening can indicate chromosome abnormality, and CMA and trio-WES may be used for the prenatal diagnosis.

Prenatal diagnosis and pregnancy outcome of fetuses with rare autosomal trisomies indicated by non-invasive prenatal testing / 中华医学遗传学杂志

OBJECTIVE@#To analyze the result of prenatal diagnosis and outcome of pregnancy for fetuses with rare autosomal trisomies (RATs) suggested by non-invasive prenatal testing (NIPT).@*METHODS@#A total of 69 608 pregnant women who underwent NIPT at Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2020 were selected as study subjects. The result of prenatal diagnosis and outcome of pregnancy for those with a high risk for RATs were retrospectively analyzed.@*RESULTS@#Among the 69 608 pregnant women, the positive rate of NIPT for high-risk RATs was 0.23% (161/69 608), with trisomy 7 (17.4%, 28/161) and trisomy 8 (12.4%, 20/161) being the most common, and trisomy 17 (0.6%, 1/161) being the rarest. For 98 women who had accepted invasive prenatal diagnosis, 12 fetal chromosomal abnormalities were confirmed, and in 5 cases the results were consistent with those of NIPT, which yielded a positive predictive value of 5.26%. Among the 161 women with a high risk for RATs, 153 (95%) were successfully followed up. 139 fetuses were ultimately born, with only one being clinically abnormal.@*CONCLUSION@#Most women with a high risk for RATs by NIPT have good pregnancy outcomes. Invasive prenatal diagnosis or serial ultrasonography to monitor fetal growth, instead of direct termination of pregnancy, is recommended.

Prenatal genetic analysis of a fetus with Miller-Dieker syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for fetus with bilateral lateral ventriculomegaly.@*METHODS@#Fetus umbilical cord blood and peripheral blood samples of its parents were collected. The fetus was subjected to chromosomal karyotyping, whilst the fetus and its parents were subjected to array comparative genomic hybridization (aCGH). The candidate copy number variation (CNV) were verified by qPCR, Application goldeneye DNA identification system was used to confirm the parental relationship.@*RESULTS@#The fetus was found to have a normal karyotype. aCGH analysis indicated that it has carried a 1.16 Mb deletion at 17p13.3, which partially overlapped with the critical region of Miller-Dieker syndrome (MDS), in addition with a 1.33 Mb deletion at 17p12 region, which is associated with hereditary stress-susceptible peripheral neuropathy (HNPP). Its mother was also found to harbor the 1.33 Mb deletion at 17p12. qPCR analysis confirmed that the expression levels of genes from the 17p13.3 and 17p12 regions were about the half of that in the normal control, as well as the maternal peripheral blood sample. Parental relationship was confirmed between the fetus and its parents. Following genetic counseling, the parents has chosen to continue with the pregnancy.@*CONCLUSION@#The fetus was diagnosed with Miller-Dieker syndrome due to the de novo deletion at 17p13.3. Ventriculomegaly may be an important indicator for prenatal ultrasonography in fetuses with MDS.