摘要
Cardio-facio-cutaneous syndrome (CFCS) is a rare genetic syndrome associated with abnormal activation of RAS-mitogen-activated protein kinase(RAS-MAPK)signal transduction pathway.Causative genes are BRAF, MAP2K1, MAP2K2 and KRAS.CFCS is an autosomal dominant disorder characterized by dysmorphic craniofacial features, congenital heart disease, dermatologic abnormalities, gastrointestinal dysfunction, failure to thrive, neurocognitive delay and epilepsy, whose phenotype overlaps with many other RASopathies.Final diagnosis of CFCS can be reached by classical presentation and genetic testing.Early diagnosis helps to evaluate risk of severe complications of specific genotype and improve prognosis of CFCS patients.At present, there is no effective treatment of CFCS although inhibitors of MEK may improve partial phenotype of CFCS animal models.Once diagnosed with CFCS, the patients need multidisciplinary assessment and treatment.
摘要
OBJECTIVE@#To explore the clinical characteristics and genetic basis of a child with Teebi hypertelorism syndrome 1 (TBHS1).@*METHODS@#A child with TBHS1 who was admitted to the Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine on July 13, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 13-year-old male, had manifested delayed growth and development. WES results revealed that he has harbored a heterozygous c.1244A>G variant of the SPECC1L gene, which was verified to be de novo in origin. The variant has not been included in the HGMD and gnomAD databases. As predicted by online software including PolyPhen-2, SIFT, and Mutation Taster, the variant may affect the function of protein domain. And PyMOL software has predicted that the structural stability of SPECC1L protein (p.Gln415Arg) might be reduced. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM6+PM1+PP4+PM2_Supporting+PP3).@*CONCLUSION@#The heterozygous c.1244A>G variant of the SPECC1L gene probably underlay the TBHS1 in this child. Above finding has expanded the genotypic and phenotypic spectrum of the SPECC1L gene and provided a basis for the clinical diagnosis of this child.
Subject(s)
Adolescent , Humans , Male , China , Computational Biology , Genomics , Genotype , Mutation摘要
Congenital disorders of glycosylation(CDG)are a group of rare inherited metabolic diseases due to defects in the glycosylation of glycoproteins and/or glycolipids.Most of them are autosomal recessive and have multisystemic manifestations, which is characterized by dysmorphic facial features, developmental delay, growth failure, hypotonia, neurological abnormalities, hypoglycemia and multisystem disfunctions.Isoelectrofocusing(IEF)analysis of transferrin(Tf)and mass spectrometry(MS)technology can diagnose some subtypes of CDG, while many currently rely on genomic sequencing technology for diagnosis.A few subtypes can be clinically relieved or even cured by treatment, but most have no effective treatment.Development of molecular, biochemical and facial recognition techniques may deepen our understanding of this disease.