RESUMEN
OBJECTIVES: Waardenburg syndrome (WS) is a rare disease characterized by sensorineural deafness and pigment disturbance. To date, almost 100 mutations have been reported, but few reports on cases with SOX10 gene deletion. The inheritance pattern of SOX10 gene deletion is still unclear. Our objective was to identify the genetic causes of Waardenburg syndrome type II in a two-generation Chinese family. METHODS: Clinical evaluations were conducted in both of the patients. Microarray analysis and multiplex ligation-dependent probe amplification (MLPA) were performed to identify disease-related copy number variants (CNVs). DNA sequencing of the SOX10, MITF and SNAI2 genes was performed to identify the pathogenic mutation responsible for WS2. RESULTS: A 280kb heterozygous deletion at the 22q13.1 chromosome region (including SOX10) was detected in both of the patients. No mutation was found in the patients, unaffected family members and 30 unrelated healthy controls. CONCLUSIONS: This report is the first to describe SOX10 heterozygous deletions in Chinese WS2 patients. Our result conform the thesis that heterozygous deletions at SOX10 is an important pathogenicity for WS, and present as autosomal dominant inheritance. Nevertheless, heterozygous deletion of the SOX10 gene would be worth investigating to understand their functions and contributions to neurologic phenotypes.
Asunto(s)
Eliminación de Gen , Factores de Transcripción SOXE/genética , Síndrome de Waardenburg/genética , Estudios de Casos y Controles , China , Cromosomas Humanos Par 22 , Femenino , Dosificación de Gen , Heterocigoto , Humanos , Lactante , Masculino , Factor de Transcripción Asociado a Microftalmía/genética , Factor de Transcripción PAX3 , Factores de Transcripción Paired Box/genética , Linaje , Adulto JovenRESUMEN
BACKGROUND:Some studies have shown that more copy number variations are present in early passage human induced pluripotent stem cells than later passage human human induced pluripotent stem cells, their parental somatic fibroblasts or human embryonic stem cells. OBJECTIVE:To investigate whether the reprogramming process itself compromises genomic stability and further explore the efficiency of induced pluripotent stem cellestablishment. METHODS:Using high-resolution Affymetrix CytoScan HD array, we compared copy number variations and loss of heterozygosity in early passage induced pluripotent stem cells with their fibroblast cellorigins from genetic epilepsy patients. RESULTS AND CONCLUSION:Compared with somatic fibroblasts from genetic epilepsy patient, there was no difference in the loss of heterozygosity between the two types of cells, but more copy number variations were present in early passage human induced pluripotent stem cells which were characterized as microduplication and involved oncogenic genes. Results demonstrate the dynamic nature of genomic abnormalities during reprogramming process and the necessity of frequent monitoring human induced pluripotent stem cells to assure their genomic stability and clinical safety.
RESUMEN
Objective To analysis the clinical manifestations of a large Spinocerebellar Ataxia 3 pedigree to pro-vide the information for the early diagnosis of Ataxia 3. Methods SCA3/ATXN3 gene was determined by using Poly-merase Chain Reaction and fragment analysis in the large pedigree members and patients ’clinical data was collected. Five patients underwent MRI imaging and fundus examination. Results There were eighteen clinical patients and twelve ATXN3 carriers in this Pedigree . In addition to ataxia, three patients presented with intellectual disability, one with cer-vical spondylosis, one with dysmyotonia, one with disorder in visual system, and seven with abnormality in autonomic ner-vous system. The MRI revealed that pons and cerebellar atrophy in some patients inordinately. Undus examination did not reveal any obvious abnormality. Conclusions The symptoms of SCA3 are heterogeneous in the same pedigree. When patients present with symptoms of cerebellar system, visual system and autonomic nervous system, or cervical spondylosis and intellectual disability, SCA3 should be considered.