Clinical features and genetic analysis of a child with EAST/SeSAME syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a EAST/SeSAME syndrome child featuring epilepsy, ataxia, sensorineural deafness and intellectual disability.@*METHODS@#A child with EAST/SeSAME syndrome who had presented at the Third Affiliated Hospital of Zhengzhou University in January 2021 was selected as the study object. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing.@*RESULTS@#Genetic testing revealed that the child has harbored compound heterozygous variants of the KCNJ10 gene, namely c.557T>C (p.Val186Ala) and c.386T>A (p.Ile129Asn), which were inherited from her mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted as likely pathogenic (PM1+PM2_Supporting+PP3+PP4; PM1+PM2_Supporting+PM3+PP3+PP4).@*CONCLUSION@#The patient was diagnosed with EAST/SeSAME syndrome due to the compound heterozygous variants of the KCNJ10 gene.

Unilateral transcranial magnetic resonance-guided focused ultrasound Pallidothalamic Tractotomy in X-linked Dystonia-Parkinsonism: A case report

@#X-linked dystonia-parkinsonism (XDP) is an adult-onset debilitating neurodegenerative disorder presenting with motor and nonmotor symptoms. The treatment options for XDP are limited. We described a patient with XDP who underwent a unilateral transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) pallidothalamic tractotomy with a one-year follow-up. The patient reported an immediate improvement in his pain after the procedure. Compared to baseline, there was an improvement in his scores in the dystonia (31%), parkinsonism (35.1%), and activities of daily living (71%) subscales at 1-year follow up. The overall improvement at one year was 46%. There were no adverse events noted. Additional studies with larger sample size and follow-up would be needed to document its long-term safety and efficacy.

Late ophthalmology findings in a X-linked juvenile retinoschisis patient / Achados oftalmológicos tardios em um paciente portador de retinosquise juvenil ligada ao cromossomo X

ABSTRACT X-linked juvenile retinoschisis (XLRS) is a vitreoretinal degeneration caused by mutations in the RS1 gene, generally characterized by bilateral maculopathy and peripheral retinoschisis leading to progressive visual loss during the first 2 decades of life and complications like retinal detachment and vitreous hemorrhage. Herein, we present late ophthalmology findings in a XLRS patient.

RESUMO A retinosquise juvenil ligada ao cromossomo X (XLRS) é uma degeneração vitreorretiniana causada por mutações no gene RS1, geralmente caracterizada por maculopatia bilateral e retinosquise periférica, levando à perda visual progressiva durante as primeiras 2 décadas de vida e complicações como descolamento de retina e hemorragia vítrea. Apresentamos aqui achados oftalmológicos tardios em um paciente com XLRS.

Analysis of FGD1 gene variant in a child with Aarskog-Scott syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect pathogenic variant of the FGD1 gene in a boy with Aarskog-Scott syndrome.@*METHODS@#Genetic variant was detected by high-throughput sequencing. Suspected variant was verified by Sanger sequencing. The nature and impact of the candidate variant were predicted by bioinformatic analysis.@*RESULTS@#The child was found to harbor a novel c.1906C>T hemizygous variant of the FGD1 gene, which has led to conversion of Arginine to Tryptophane at codon 636(p.Arg636Trp). The same variant was found in his mother but not father. Based on the American College of Medical Genetics and Genomics guidelines, the c.1906C>T variant of FGD1 gene was predicted to be likely pathogenic(PM1+PM2+PM5+PP2+PP3+PP4).@*CONCLUSION@#The novel c.1906C>T variant of the FGD1 gene may underlay the Aarskog-Scott syndrome in this child. Above finding has enabled diagnosis for the boy.

Genetic study of an X-linked agammaglobulinemia pedigree caused by an BTK mutation / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic pathogenesis of X-linked agammaglobulinemia in two patients for clinical diagnosis and family counseling.@*METHODS@#Data was collected from the patients' family including clinical information, blood immunoglobulin level, as well as classification and subgrouping of B lymphocytes. Gene mutations were screened by whole exome sequencing (WES) through next-generation sequencing (NGS), the result was verified with Sanger sequencing.@*RESULTS@#A BTK c.1627T>C (p.Ser543Pro) variant was found in the pedigree. The phenotype and variant have co-segregated in the pedigree. The variant was not found in population database. The variant has affected in the kinase domain which contained no benign variants and is harmful as predicted through bioinformatic analysis.@*CONCLUSION@#BTK c.1627T>C (p.Ser543Pro) is a pathogenic variant contributing to X-linked agammaglobulinemia in this pedigree. Above finding has provided reproduction guidance for this family.

Identification of a novel variant of NHS gene underlying Nance-Horan syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a pedigree affected with Nance-Horan syndrome.@*METHODS@#Clinical manifestation of the patients was analyzed. Genomic DNA was extracted from peripheral blood samples of the pedigree members and 100 unrelated healthy controls. A panel of genes for congenital cataract was subjected to next-generation sequencing (NGS), and candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of American College of Medical Genetics and Genomics (ACMG). mRNA expression was determined by reverse transcriptase-PCR (RT-PCR). Linkage analysis based on short tandem repeats was carried out to confirm the consanguinity.@*RESULTS@#A small insertional variant c.766dupC (p.Leu256Profs*21) of the NHS gene was identified in the proband and his affected mother, but not among unaffected members and the 100 healthy controls. The variant was unreported in Human Gene Mutation Database (HGMD) and other databases. Based on the ACMG guideline, the variant is predicted to be pathogenic (PVS1+PM2+PM6+PP4).@*CONCLUSION@#The novel variant c.766dupC of the NHS gene probably underlay the X-linked dominant Nance-Horan syndrome in this pedigree.

Clinical features and genetic analysis of a child with late-onset immune dysregulation, polyendocrinopathy, enteropathy, X-Linked syndrome / 中华医学遗传学杂志

OBJECTIVE@#To report on the clinical features and result of genetic testing for a child featuring immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.@*METHODS@#Clinical records, genetic testing, laboratory investigation and treatment of the child were summarized in addition with a comprehensive review of the literature.@*RESULTS@#The 3-year-old boy was administered due to intractable diarrhea, recurrent infections, liver dysfunction and failure to thrive, though no diabetes or skin disorder was observed. Laboratory testing showed elevated liver enzymes and total IgE, decreased albumin and electrolyte imbalance. Gastrointestinal endoscopy revealed erosion and granules in the duodenum, and edema in the terminal ileum and colon. Biopsies showed villous atrophy in the duodenum and terminal ileum. Genetic testing revealed that the patient has carried a missense c.1087A>G (p.I363V) variant in the exon 10 of the FOXP3 gene. He was treated with enteral and parenteral nutrition, anti infection and Sirolimus, and was waiting for hemopoietic stem cell transplantation.@*CONCLUSION@#Although IPEX syndrome usually occur during infancy, it should not be ruled out solely based on the age, and its presentation can be variable. For male children with refractory diarrhea, autoimmune disorder and growth retardation, the diagnosis should be suspected and confirmed by genetic testing.

Prevalence and clinical characteristics of X-linked hypophosphatemia in Paraná, southern Brazil

ABSTRACT Objective: The aim of this cross-sectional study was to estimate the prevalence of XLH in Paraná, a state in southern Brazil, and report the clinical features and complications of the disease. Materials and methods: We invited all endocrinologists (n = 205), nephrologists (n = 221), orthopedic surgeons (n = 1020), and pediatricians (n = 1000) in Paraná to fill out an electronic survey with information on patients with X-linked hypophosphatemia (XLH), and searched the records of the state's health department for all calcitriol prescriptions in 2018. Results: In all, 244 (10%) specialists responded to the email, of whom 18 (7.4%) reported to be taking care of patients with XLH and answered the online survey. A total of 57 patients with XLH were identified (prevalence 5 per million inhabitants). The median age at diagnosis was 22 years, and 42.2% were children and adolescents. Fifteen patients had genetic testing showing a PHEX mutation. Overall, 91.2% had bone deformities, 30.8% had a history of fragility fractures, and 22.4% had renal complications. Conclusion: This study demonstrated a prevalence of XLH of 5 cases per million inhabitants in the state of Paraná, a rate lower than the one reported in other countries. Manifestations of renal calcification and bone fragility were frequent among the patients. This is the first epidemiological study evaluating the prevalence and clinical presentation of XLH in Latin America.

Nueva mutación identificada en el gen FOXP3 en lactante menor con diarrea crónica como manifestación de enteropatía autoinmune - síndrome IPEX / New mutation in FOXP3 gene identified in an infant with chronic diarrhea as manifestation of autoinmune enteropathy - IPEX syndrome

INTRODUCCIÓN: El síndrome IPEX (inmunodesregulación, poliendocrinopatía y enteropatía autoinmune ligada a X) causado por mutaciones en el gen FOXP3, se caracteriza por diarrea prolongada, alteraciones endocrinológicas y dermatitis. El tratamiento consiste en la administración de medicamentos inmunosupresores, siendo el trasplante de médula ósea la única cura potencial. OBJETIVO: Describir una nueva mutación del gen FOXP3, así como los hallazgos y evolución de un paciente con síndrome IPEX. CASO CLÍNICO: Lactante menor masculino que debutó al mes de vida con diarrea cró nica, falla intestinal e infecciones recurrentes. Exámenes de laboratorio y biopsia intestinal sugerentes de enteropatía autoinmune. Durante el seguimiento, el paciente presentó refractariedad al manejo inmunosupresor con esteroides, ciclosporina y tacrolimus, falleciendo a los 7 meses de edad por complicaciones vasculares. Antecedente familiar por línea materna de múltiples muertes en hombres menores de 1 año. Ante la sospecha de síndrome IPEX se realizó exoma en trío que reportó una mutación probablemente patogénica en el gen FOXP3. CONCLUSIÓN: Se documentó una nueva mutación del gen FOXP3 en paciente con síndrome IPEX. A pesar de la baja prevalencia de esta enfermedad, es importante el reconocimiento de síntomas no específicos pero sugerentes del diagnóstico.

INTRODUCTION: The IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syn drome is caused by the mutations of the FOXP3 gene, characterized by persistent diarrhea, endo crine disorders, and dermatitis. The treatment is the administration of immunosuppressive drugs, where hematopoietic stem cell transplantation is the only potential cure. OBJECTIVE: To describe a new FOXP3 gene mutation, as well as the findings and evolution of a patient with IPEX syndrome. CLINICAL CASE: Male infant presenting at one month of age with chronic diarrhea, intestinal failure, and recurrent infections. Lab tests and intestinal biopsy suggested autoimmune enteropathy. During follow-up, the patient presented resistance to immunosuppressive treatment with corticosteroids, cyclosporine, and tacrolimus, dying at 7 months of age due to vascular complications. He had a ma ternal family history of multiple deaths of men under 1 year of age. IPEX syndrome was suspected therefore a trio whole-exome sequencing was performed that showed a probably pathogenic FOXP3 gene mutation. CONCLUSION: A new FOXP3 gene mutation is reported in a patient with IPEX syndro me. Despite the low prevalence of this disease, it is important to recognize non-specific but suggestive symptoms for its diagnosis.

La citometría de flujo como auxiliar en el diagnóstico de las inmunodeficiencias primarias humorales / Flow-cytometry as an auxiliary in the diagnosis of primary humoral immunodeficiencies

Resumen Antecedentes: Las deficiencias de anticuerpos abarcan un amplio espectro de patologías y constituyen aproximadamente 50 % de las inmunodeficiencias primarias; con la citometría es posible evaluar el estado inmunológico de forma rápida, efectiva y a bajo costo. Objetivo: Evaluar mediante citometría de flujo, las células de pacientes con tres tipos de inmunodeficiencias primarias humorales. Método: Mediante citometría de flujo se analizaron muestras de sangre de pacientes y sujetos sanos con distintos anticuerpos monoclonales. Resultados: Mediante diversas tinciones se demostró disminución severa de linfocitos B en pacientes con agammaglobulinemia ligada al cromosoma X, la falta de expresión de CD154 en pacientes con síndrome de hiperinmunoglobulina M y heterogeneidad de subpoblaciones de linfocitos B en pacientes con inmunodeficiencia común variable. Conclusión: Con la citometría de flujo es posible realizar el diagnóstico temprano de inmunodeficiencias primarias con un nivel de confianza elevado y, en muchos casos, identificar los genes implicados.

Abstract Background: Antibody deficiencies encompass a wide spectrum of pathologies and constitute approximately 50 % of primary immunodeficiencies; with cytometry, it is possible to evaluate the immune status rapidly, effectively and at low cost. Objective: To assess, by means of flow cytometry, the cells of patients with three types of primary humoral immunodeficiencies. Method: Using flow cytometry, blood samples from patients and healthy subjects were analyzed with different monoclonal antibodies. Results: Using various stains, a severe decrease in B lymphocytes was shown in patients with X-linked agammaglobulinemia, as well as a lack of CD154 expression in patients with hyper-immunoglobulin M syndrome, and heterogeneity of B lymphocyte subpopulations in patients with common variable immunodeficiency. Conclusion: Flow cytometry enables early diagnosis of primary immunodeficiencies with a high level of confidence and, in many cases, identification of the genes involved.

Norrie disease caused by a c.361C>T missense variant of the NDP gene in a pedigree / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a pedigree affected with Norrie disease.@*METHODS@#Four individuals from the core family of the proband were subjected to whole exome sequencing in order to identify the pathological variant. Sanger sequencing was used to verify the finding among 7 additional members from the pedigree.@*RESULTS@#The proband and other 3 male patients have all carried a hemizygote c.361C>T (p.Arg121Trp) missense variant of the NDP gene, for which his mother, grandmother and two younger female cousins were heterozygous carriers. The same variant was not detected among unaffected males. Above results conformed to a X-linked recessive pattern of inheritance.@*CONCLUSION@#The missense variant c.361C>T of the NDP gene probably underlies the Norrie disease in this pedigree.

Peripheral blood stem cell transplantation from HLA-mismatched unrelated donor or haploidentical donor for the treatment of X-linked agammaglobulinemia / 中国当代儿科杂志

Allogeneic stem cell transplantation (allo-SCT) is currently the only curative option for patients with X-linked agammaglobulinemia (XLA). In this study, patient 1 aged 4 years who underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from HLA-mismatched unrelated donor; patient 2 aged 24 years (childhood onset) with primary cutaneous acral CD8 T cell lymphoma who underwent allo-PBSCT from haploidentical relative donor. Both were treated by reduced toxicity myeloablative conditioning with post-transplantation cyclophosphamide (PTCy), anti-thymocyte globulin (ATG), methotrexate (MTX) and cyclosporine (CsA) for graft-versus-host-disease (GVHD) prophylaxis. In patient 1, neutrophil and platelet engraftment were observed on day 11 post-transplantation; the donor chimerism dropped on day 90 post-transplantation, and recovered on day 150 with donor lymphocyte infusion (DLI). In patient 2, neutrophil and platelet engraftment were observed on days 20 and 87 post-transplantation respectively, with complete donor chimerism on day 30 post-transplantation. The serum levels of IgG, IgM and IgA and the percentage of CD19 B cells in peripheral blood of patients 1 and 2 returned to normal within 2 months and more than 1 year after transplantation respectively. There was no evidence of acute GVHD for the two patients. Patient 1 developed a limited type of skin chronic GVHD after DLI, which disappeared after anti-GVHD treatment. This is the first report of successful treatment for two XLA patients using PTCy with allo-PBSCT from HLA-mismatched unrelated donor or haploidentical donor, combining with improved conditioning, which expands the pool of eligible donors for patients with XLA.

Diagnóstico genético de pacientes con agammaglobulinemia primaria atendidos en centros peruanos de tercer nivel / Genetic diagnosis of patients with primary agammaglobulinemia treated at third level peruvian centers

Las agammaglobulinemias primarias (AP) resultan de alteraciones específicas en las células B, lo cual, conduce a baja producción de anticuerpos. La sospecha diagnóstica se establece con el antecedente de infecciones a repetición, inmunoglobulinas bajas y la ausencia linfocitos B CD19+. El diagnóstico se confirma mediante el análisis genético y la detección de una mutación ligada en el cromosoma X o autosómico recesiva o dominante. En Perú, no hay literatura sobre AP ni reportes sobre el genotipo de los pacientes con sospecha de AP. Bajo este escenario, se realizó un estudio que describió el genotipo de pacientes con sospecha de AP. Se encontraron 20 pacientes con mutaciones en el gen BTK y una mutación autosómica recesiva IGHM. Se hallaron 13 mutaciones hereditarias y siete mutaciones de novo. Se concluye que las AP son, en su mayoría, mutaciones en el gen BTK que corresponden con AP ligadas al cromosoma X.

Primary agammaglobulinemia result from specific alterations in B cells, which lead to low antibody production. Diagnostic suspicion is established with a history of repeated infections, low immunoglobulins, and absence of CD19+ B lymphocytes. The diagnosis is confirmed by genetic analysis and the detection of a mutation linked to the X or autosomal recessive or dominant chromosome. In Peru, there is no literature on primary agammaglobulinemia and no reports on the genotype of patients with suspected primary agammaglobulinemia. Under this scenario, a study was performed to describe the genotype of patients with suspected primary agammaglobulinemia. Twenty (20) patients were found with mutations in the BTK gene and an autosomal recessive IGHM mutation. Thirteen (13) hereditary mutations and seven de novo mutations were found. It is concluded that the group of primary agammaglobulinemia are mostly mutations in the BTK gene, corresponding to X-linked agammaglobulinemia.

Urrets-Zavalia Syndrome following cataract surgery in a case of anterior megalophthalmos / Síndrome de Urrets-Zavalia após cirurgia de catarata em um caso de megaloftalmo anterior

ABSTRACT Intraoperative and postoperative cataract surgery in eyes with anterior megalophthalmos are challenging procedures. Herein we describe the case of a 53-year-old male with anterior megalophthalmos who developed unilateral Urrets-Zavalia Syndrome following cataract surgery.

RESUMO O intraoperatório e o pós-operatório de cirurgia de catarata em olhos com megaloftalmo anterior é desafiador. Descrevemos o caso de um homem de 53 anos com megaloftalmo anterior que desenvolveu a Síndrome de Urrets-Zavalia unilateral após cirurgia de catarata.

CHILD syndrome: successful treatment of skin lesions with topical lovastatin and cholesterol lotion

Abstract: CHILD syndrome (Congenital Hemidysplasia, Ichthyosiform erythroderma, Limb Defects) is a rare X-linked dominant disease. The authors report a 2-month-old patient presenting with typical features of CHILD syndrome that was treated with a topical solution containing cholesterol and lovastatin, with complete clearance of her CHILD nevus. The changes in skin lipid metabolism that explain the CHILD ichthyosiform nevus and their correction through topical application of cholesterol and lovastatin are discussed.

Propiedades psicométricas de la escala EMUN-AR determinadas mediante el análisis de Rasch / Psychometric variables of the EMUN-AR scale using Rasch analysis

Resumen Introducción. Las escalas de autorreporte se han considerado útiles para evaluar y vigilar los síntomas de la enfermedad maníaco-depresiva. Uno de estos instrumentos, la escala de medición de la enfermedad maníaco-depresiva mediante autorreporte (EMUN-AR), no se ha validado aún. Objetivo. Validar la escala EMUN-AR usando el modelo de Rasch. Materiales y métodos. La escala EMUN-AR mide 26 ítems que evalúan por dimensiones los síntomas de la enfermedad maníaco-depresiva en tres categorías: frecuencia, intensidad y grado de molestia causada. Para evaluar las propiedades psicométricas de la escala, se efectuaron análisis factoriales exploratorios con el fin de tener una aproximación de su estructura latente, y se usaron modelos de Rasch que incluyeron la 'unidimensionalidad', la confiabilidad, el ajuste de ítems, el ordenamiento de umbrales, y los mapas de personas e ítems. Resultados. Se seleccionó una muestra de 267 pacientes hospitalizados, 204 de los cuales había sufrido un episodio maníaco (76,4 %) y estaba recibiendo tratamiento farmacológico. Se encontró una estructura factorial que puede resumirse en cuatro dominios: activación, inhibición, ideas depresivas e inadaptación. El análisis de Rasch evidenció la unidimensionalidad en los factores, adecuados valores de confiabilidad, buen ajuste de los 26 ítems en general (excepto en el ítem que mide las ideas de muerte o suicidio), un funcionamiento deficiente del sistema de calificación de los ítems y un cubrimiento limitado de los síntomas de la enfermedad correspondientes a las formas atenuadas. Conclusión. Se modificó la escala original en dos aspectos: se ajustó un ítem cuyos indicadores marginales tenían mal ajuste y se redujo el número de categorías. En su forma actual, el instrumento es apropiado para medir las formas graves de la enfermedad maníaco-depresiva, mas no así las atenuadas.

Abstract Introduction: Self-report scales have been considered to be useful for evaluating and monitoring symptoms of manic-depressive illnesses. The EMUN-AR scale is one of such scales but it has not been validated. Objective: To validate the EMUN-AR scale using Rasch models. Materials and methods: The EMUN-AR scale measures 26 items to assess comprehensively symptoms of manic-depressive illnesses in three domains: Frequency, severity, and level of disturbance caused by the symptoms. To test the psychometric properties of this scale, we used the exploratory factorial and Rasch analyses. The Rasch analysis included unidimensionality, reliability, item fit, threshold ordering, and person-item maps. Results: The study included 267 hospitalized patients, most of them with a manic episode diagnosis (n=204, 76.4%), and receiving pharmacological treatment. The factor structure was summarized in four domains: Activation, inhibition, depressive ideation, and maladaptive behavior. The Rasch analysis supported unidimensionality of the EMUN-AR factors, satisfactory levels of reliability, and appropriate item fit, except for one of the items measuring death or suicidal thoughts. However, the scale did not measure adequately the mild forms of the illness given its redundant and unordered thresholds. Conclusion: The EMUN-AR was modified in two aspects: An item whose marginal indicators were poorly adjusted and the reduction in the number of categories. In its current form, the EMUN-AR is appropriate for measuring severe forms of the illnesses, but it does not adequately measure the mild forms of manic-depressive illnesses.

Clinical features and gene mutation spectrum in children with sideroblastic anemia / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features and gene mutation spectrum of children with sideroblastic anemia (SA) and the clinical value of targeted next-generation sequencing in the molecular diagnosis of children with SA.@*METHODS@#Clinical data were collected from 36 children with SA. Targeted next-generation sequencing was used to detect mutations in SA-related pathogenic genes and genes associated with heme synthesis and mitochondrial iron metabolism. The association between genotype and clinical phenotype was analyzed.@*RESULTS@#Of the 36 patients, 32 had congenital sideroblastic anemia (CSA) and 4 had myelodysplastic syndrome with ring sideroblasts (MDS-RS). Mutations in CSA-related genes were detected in 19 children (19/36, 53%), among whom 9 (47%) had ALAS2 mutation, 4 (21%) had SLC25A38 mutation, and 6 (32%) had mitochondrial fragment deletion. No pathogenic gene mutation was detected in 4 children with MDS-RS. Among the 19 mutations, 89% (17/19) were known mutations and 11% (2/19) were novel mutations. The novel mutation of the ALAS2 gene c.1153A>T(p.I385F) was rated as "possibly pathogenic" and the novel mutation of the SLC25A38 gene c.175C>T(p.Q59X) was rated as "pathogenic".@*CONCLUSIONS@#ALAS2 and SLC25A38 gene mutations are commonly seen in children with CSA, but mitochondrial gene fragment deletion also accounts for a relatively high proportion. For children with hypoplastic anemia occurring in infancy, mitochondrial disease should be considered.

Analysis of Correlation of WAS Gene Mutations with Clinical Phenotype / 中国实验血液学杂志

OBJECTIVE@#To investigate the gene mutation of patients with WAS gene defect and its correlation with clinical manifestations.@*METHODS@#Thirty-one patients consulted in Children's Hospital of Soochow University from January 2013 to February 2018 were enrolled in this study. The hot pot mutations of WAS gene in 31 patients were detected and related clinical phenotypes were analyzed retrospectively.@*RESULTS@#All patients were male. The median onset age was 1 month (range, 0-83 months). Nine mutants were reported as novel mutations among 25 mutants detected in 31 patients, including c.1234_1235dupCC, c.1093-1097delG, c.28-30dupC, c.436G>T, c.273 + 10_273 + 11dupCC, c.995_996insG, c.1010T>A, c.332_333delCC and c.683C>T mutations. There were 25 cases of classic WAS which mutations included missense mutation, deletion mutation, insertion mutation, splicing mutation and nonsense mutation, 2 cases of X-linked thrombocytopenia (XLT) were induced by missense mutation, 1 case of intermittent X-linked thrombocytopenia (IXLT) was induced by splicing mutation, 2 cases of X-linked pancytopenia were induced by missense mutation. Intravenous immunoglobulin (IVIG) and glucocorticoid therapy in IXLT patient was effective, and remission could be sustained, platelets could be increased in the short-term in treated XLT patients, but only a small part of classic WAS patients(8.0%) showed transient response to it, the IVIG and glucocorticoid therapy did not improve the status of platelet in XLP patients. Immune laboratory examination showed that CD3 was decreased in 60.0% patients, CD19 was decreased in 12.0% patients, and CD56CD16 in 4 patients was decreased, accounting for 16.0%. Out of 24 patients, 22 patients were alive after treated with hematopoietic stem cell transplantation (HSCT), 4 patients who were not given HSCT died of brain bleeding and severe infection, 1 patient diagnosed as IXLT got remission and survived.@*CONCLUSION@#WAS gene defect is an important basis for the diagnosis of WAS and related diseases. IVIG plus glucocorticoid therapy is less effective for fewer patients, the HSCT is an effective treatment for WAS.

Genetic analysis and prenatal diagnosis for a pedigree affected with X-linked Norrie disease / 中华医学遗传学杂志

OBJECTIVE@#To detect mutation of NDP gene in a pedigree affected with Norrie disease.@*METHODS@#Sanger sequencing was used to analyze the NDP gene at Xp11.3. Prenatal diagnosis was performed on amniotic fluid sample after the causative gene was detected.@*RESULTS@#Sanger sequencing has revealed a c.2T>C (p.M1T) missense mutation of the NDP gene in the proband and the fetus. The same variation was not found in ClinVar and HGMD database.@*CONCLUSION@#The c.2T>C mutation of the NDP gene probably underlies the Norrie disease in this pedigree.