Novel NR2F1 variant identified by whole-exome sequencing in a patient with Bosch–Boonstra–Schaaf optic atrophy syndrome

Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS) is an extremely rare autosomal dominant disorder characterized by intellectual disability, developmental delay, seizures, hypotonia, hearing loss, and optic nerve atrophy. This syndrome is caused by loss-of-function variants in the nuclear receptor subfamily 2 group F member 1 ( NR2F1 ) gene. To date, approximately 80 patients have been reported with BBSOAS. Here, we describe a 3-year-old infant with delayed development, intellectual disability, strabismus, nystagmus, and optic atrophy with well-characterized features associated with BBSOAS. Whole-exome sequencing revealed a novel heterozygous missense mutation (NM_005654.6:c.437G>A, p.Cys146Tyr) in the NR2F1 gene. This missense variant is predicted to be deleterious by the protein prediction tools (SIFT, PolyPhen-2, and MutationTaster). To the best of our knowledge, this is the first patient with BBSOAS reported from Turkey.

Boonsta-Bosch-Schaff optic atrophy syndrome with infantile spasm: A case and literatures review / 解放军医学杂志

Objective To report a case of Boonsta-Bosch-Schaff optic atrophy syndrome (BBSOAS) with infantile spasm, its clinical features as well as diagnosis and treatment process, and review the relevant literature. Methods Retrospectively analyze the clinical data of a case of BBSOAS with infant spasm patient in the First Medical Center of PLA General Hospital, retrieve the databanks of online human Mendelian genetic database (OMIM), PubMed, CNKI and Wanfang Medical Online, explore the clinical characteristic of BBSOAS with infant spasm patients, the relationship between the phenotype - genotype, and the therapeutic effect. Results The patient was a 9-month-old boy admitted to hospital due to "intermittent convulsions for 4 months". The growth and development of the child delayed, gaze following was poor; fundus examination showed pale optic disc (atrophy, small optic disc), spasm attack, and electroencephalogram indicated hypsarrhythmia. Genetic test found de novo missense mutation in NR2F1 gene c.383G>A (p.YS128tyr), so diagnosed as BBSOAS and Infantile spasms. The spasticity was not controlled and hypsarrhythmia was still existed in electroencephalogram after adrerrmrticotropic hormone (ACTH) and a variety of antiepileptic drugs were administered. Fever occurred 2 weeks after out of hospital oral perampanel, spasms was completely controlled after the febrile retrograde. A total of 9 English references were obtained by searching multiple databases and manual screening, and a total of 46 cases of BBSOAS were found, among which 9 cases were complicated with infantile spasms. All the amino acid changes caused by NR2F1 gene mutation were located in DNA-binding domain, and optic nerve atrophy or/and hypoplasia were observed. Conclusions The new missense mutation of NR2F1 gene c.383G>A that caused BBSOAS and infantile spasm is no literature report before. In case of optic atrophy or hypoplasia associated with spasm in infants and young children, the doctor should consider the possibility of BBSOAS, and do the genetic examination if necessary. Perampanel may be a potential drug for spasm control in such children.

Treatment of Disseminated Sclerosis Combining Disease and Syndrome with Traditional Chinese Medicine / 中华中医药杂志

Disseminated sclerosis(DS) is an autoimmune demyelinating disease of the central nervous system(CNS) that attacks generally the youth.The common symptoms of DS are hypopsia,paralysis,abnormal sense,urine deposited,dysfunction of bowels,etc.Sometimes MS also injures neural advanced functions.Traditional Chinese Medicine(TCM) mainly defines DS as "atrophy syndrome" according to its clinic symptoms.During acute relapsing period,most DS patients present deficiency of yin of both the kidney and liver,occurring with blood stasis and phlegm.Moreover,high dose methylprednisolone can activate pathogenic fire to damage the yin that aggravates deficiency of yin.Along with repeated relapse and evolvement of DS,the body's condition will change into syndrome of deficiency of both the yin and yang.So,the drugs of nourishing both the kidney and liver yin,activating blood circulation and clearing phlegm should be applied first to treat DS. Besides,the drugs of clearing heat,activating yang,motivating flow of qi,dredging the Fu-organ,invigorating blood and regulating liver-qi should also be used according to the different syndromes.