Diagnostic value of array-based single nucleotide polymorphisms comparative genomic hybridization in Angelman syndrome

Abstract

Objective To analyze the genotype-phenotype correlations of Angelman syndrome(AS), and to discuss the advantage of applying array-based single nucleotide polymorphisms comparative genomic hybridization(SNP aCGH)in diagnosis of AS. Methods Examination of electroencephalogram(EEG)and intelligence quotient(IQ) evaluation were done for 11 cases diagnosed as AS clinically.Gesell scares were chosen as the evaluation criterion of IQ.The screening techniques was methylation polymerase chain reaction(MS-PCR), then SNP aCGH was used to make genetic diagnosis. Results (1)Eleven cases of AS were confirmed: 1 case had UPD(uniparental disomy), 10 cases were type of deletion, from which 6 cases were deletion(Ⅱ), 4 cases were deletion(Ⅰ). (2)The copy number variations were detected in the region of 15q11-q13, which contained genes like MKRN3, MAGEL2, NDN, SNRPN, SNURF, GABRB3, GABRA5, GABRG3, UBE3A, OCA2, ATP10A.To search online Mendelian inheritance in man, genes above were correlated with AS manifestation.(3)All cases of deletion were 3-5 standard deviation(SD) in weight and height to normal children at the same age and with the same sex, while UPD was below 1.5 SD.Gesell scares showed that the deletion(Ⅰ) was the most serious in mental retardation, deletion(Ⅱ) was moderate, and the UPD was mild.Eight cases were hypopigmentation, and one was the UPD.EEG revealed that 1 case of deletion(Ⅰ) and the UPD were spike occasionally, another one deletion(Ⅰ) was limit EEG.The rest cases displayed slow and spike waves paroxysmally, with amplitude of medium or high, 2.5-3.0 Hz. Conclusions Not only can SNP aCGH make a diagnosis of AS but discriminate the types of genetic pathology.Since different type contributes to a diverse of clinical features and the rate of recurrence is also different, it is significant for family genetic consultation.Moreover, the technology is advantageous for the study on the pathogenesis and gene function. Key words: Array-based single nucleotide polymorphisms comparative genomic hybridization; Angelman syndrome; Genotype; Phenotype