Precise Microdeletion Detection of Prader-Willi Syndrome with Array Comparative Genome Hybridization

摘要

Objective Prader-Willi Sydrome(PWS) is a human disorder related to genomic imprinting defect on 15q11-13.It is characterized by a series of classic features such as hypotonia,hyperphagia,obesity,osteoporosis,typical facial and body dysmorphosis,hypogonadism,mental and behaviour disorders.Our study was designed to precisely detect the microdeletions, which accounts for 65%-70%of the PWS.Methods Physical and laboratory examinations were firstly performed to diagnose PWS clinically,and to discover novel clinical features.Then the patient was screened with bisulfite-specific sequencing and precisely delineated through high-density array CGH.Results With the bisulfite-specific sequencing,the detected CpG island in the PWS critical region was found homozygously hypermethylated.Then with array CGH,a 2.22 Mb typeⅡmicrodeletion was detected,covering a region from MKRN3,MAGEL2,NDN,PWRN2,PWRN1,C12orf2, SNURF-SNRPN,C/D snoRNAs,to distal of UBE3A.Conclusions Array CGH,after the fast screening of Bisulfite-specific sequencing,is a feasible and precise method to detect microdeletions in PWS patients.A novel feature of metacarpophalangeal joint rigidity was also presented,which is the first time reported in PWS.