Clinical And Genetic Analysis Of 10 Chinese Patients With Recurrent Fever And MEFV Gene Variation And A Case Report Of BCL11B Mutation Induced Neurodevelopmental Disorder And Literature Review

PART ? CLINICAL AND GENETIC ANALYSIS OF 10 CHINESE PATIENTS WITH RECURRENT FEVER AND MEFV GENE VARIATIONObjective: To explore the key points of diagnosis for familial Mediterranean fever(FMF)and the genotype-phenotype correlations.Methods: The genetic testing and clinical manifestations of 10 Chinese patients with MEFV gene variation affected by recurrent fever were retrospectively analyzed.The key points of diagnosis of familial Mediterranean fever(FMF)and the genotype-phenotype correlations were summarized by reviewing related articles.Results: Four MEFV gene variations were identified in 10 patients,including G304 R,E148Q,L110 P,P369S,and R408 Q.In 10 patients,4 cases had homozygous variation(40%),2 cases had heterozygous variation(20%),and 4 cases had complex variation(40%).According to the criteria of Tel Hashomer,1 patient had a definite diagnosis of FMF and 3 patients had probable diagnosis of FMF,while on the basis of Turkish Pediatric criteria,8 of the 10 patients had clinical diagnosis of FMF.Conclusions: FMF reflects a clinical diagnosis,which can be supported but not excluded by genetic testing.Patients who are homozygous for M694 V mutation are at risk of early onset disease and developing a severe phenotype with very high probability;while the E148 Q variant is common,with unknown pathogenic significance,and when it is the only MEFV variant in patients,it does not support the diagnosis of FMF.More and further researches are still needed.PART ? A CASE REPORT OF BCL11 B MUTATION INDUCED NEURODEVELOPMENTAL DISORDER AND LITERATURE REVIEWObjective: To analyze the clinical,immunological and genetic features of a child with BCL11 B mutation induced neurodevelopmental disorder.Methods: The clinical data and genetic test of a child with BCL11B mutation hospitalized in the Department of Rheumatology and Immunology in Children's Hospital of Chongqing Medical University in December 2018 were extracted and analyzed.The literature was searched with "BCL11B mutation" and "immunodeficiency 49" as key words in Chinese databases and Pubmed until January 2019 was reviewed.Results: A male patient aged 3 years and 11 months with facial dysmorphisms and delayed language and motor development was admitted due to neurodevelopmental retardation over two years.Laboratory tests showed normal human immunoglobulin(Ig G 12.90 g/L,Ig A 1.02 g/L,Ig M 1.15 g/L,Ig E 532 000 U/L),and proliferation of T and B cells.Trec(228)is slightly lower.The lymphocyte subsets revealeda reduced percentage of B cells(0.108)but normal absolute numbers(0.574×10-3/ L),and an increased percentage(0.828)as well as absolute numbers(4.415 × 10-3 / L)of T cells.A heterozygous BCL11 B mutation was detected by sanger sequencing,showing a de novo frameshift mutation c.1887_c.1893 del CGGCGGG in exon 4.Two papers were found which were all in English,with total of 14 patients(13 patients with complete information).Thirteen mutations were reposed,including 7 frameshift,2 nonsense,2 missense,and 2 chromosomal rearrangements;Thirteen patients had heterozygous mutations.All patients had delayed language and motor development and facial dysplasia which were mainly hypertelorism,thin eyebrows and small palpebral fissures.Some patients had dental anomalies,ametropia and allergy,and a few were combined with immune impairment,but without overt signs of immunodeficiency.Only one patient had multisystem anomalies and profound immune deficiency.Conclusions: BCL11 B is essential for development of the nervous and the immune system.In this study,the de novo mutation of BCL11 B gene resulted in neurodevelopmental and immunological disorders.