Expanded Carrier Screening For Eleven Recessive Diseases During Early Pregnancy:A Multi-center Study In China

ObjectiveThe study aimed to realize the carrier status,the common variants of eleven recessive diseases,and to suggest a preliminary model of carrier screening suitable for pregnancy women in China.MethodsThis multicenter prospective study is conducted by Peking Union Medical College Hospital combined with other 8 hospitals to eleven recessive diseases with clear association between genotype and phenotype for early pregnancy population in China,which including Dystrophie Mysculaire de Duchenne,Spinal Muscular Atrophy,Wilson’s Disease,Alpha-thalassemia,Beta-thalassemia,Hemophilia B,Phenylketonuria,Glycogen Storage Disease,Galactosemia,autosomal recessive deafness 1 A,and autosomal recessive deafness type 4.The eligible couples could participate in the study by simultaneous detection or sequential detection.The samples were tested by target acquisition combined with high-throughout sequencing technology.Our team informed and counseled the results to each participant,especially for high-risk couples.The high-risk couples could choose prenatal diagnosis,and receive posttest genetic counseling.And our team would follow up all pregnancy outcomes.Main resultsOur study enrolled 5957 people,including 2924 couples and 109 pregnancy women.All participants were from 31 provinces,and 27 nationalities,which mainly in the Han population(94.12%).Among all enrolled couples,2909 couples were detected simultaneously and other 15 couples detected sequentially.The test turnaround time of two screening models was 26 days and 50 days,respectively.Among enrolled participants,the overall carrier rate of target diseases was 14.17%(844/5957),which the top two carrier rates were thalassemia(3.65%)and autosomal recessive deafness(5.22%).For the carrier rates of target diseases,no significant differences were observed in the North and South(P>0.05),excluding the thalassemia(P<0.001).A total of 163 variants were detected,among which 14 variants had allele frequency over 0.1%,accounting for 66.9%(597/892)of all detected variants.The top four variants were-a3.7(110,0.92%),GJB2:c.235delC(108,0.91%),SLC26A4:c.919-2A>G(92,0.77%,and SMN1 EX7del(84,0.71%).Out of all 15 high-risk couples,7 couples(46.67%)chose prenatal diagnosis.Four cases of fetus were diagnosed with target resessive diseases,namely 2 cases of autosomal recessive deafness 4,1 case of autosomal recessive deafness 1 A,and 1 case of spinal muscular atrophy,which only spinal muscular atrophy is a severe recessive disease.In the end,these four couples decided to induced abortion.ConclusionGiven low incidence about 1 in 3,000 cases of severe recessive diseases,we should be cautious of extended carrier screening in China.