Results of carrier screening for Spinal muscular atrophy among 35 145 reproductive-aged individuals from Dongguan region / 中华医学遗传学杂志

OBJECTIVE@#To carry out carrier screening for Spinal muscular atrophy (SMA) in reproductive-aged individuals from Dongguan region and determine the carrier frequency of SMN1 gene mutations.@*METHODS@#Reproductive-aged individuals who underwent SMN1 genetic screening at the Dongguan Maternal and Child Health Care Hospital from March 2020 to August 2022 were selected as the study subjects. Deletions of exon 7 and 8 (E7/E8) of the SMN1 gene were detected by real-time fluorescence quantitative PCR (qPCR), and prenatal diagnosis was provided for carrier couples by multiple ligation-dependent probe amplification (MLPA).@*RESULTS@#Among the 35 145 subjects, 635 were found to be carriers of SMN1 E7 deletion (586 with heterozygous E7/E8 deletion, 2 with heterozygous E7 deletion and homozygous E8 deletion, and 47 with sole heterozygous E7 deletion). The carrier frequency was 1.81% (635/35 145), with 1.59% (29/1 821) in males and 1.82% (606/33 324) in females. There was no significant difference between the two genders (χ² = 0.497, P = 0.481). A 29-year-old woman was found to harbor homozygous deletion of SMN1 E7/E8, and was verified to have a SMN1∶SMN2 ratio of [0∶4], none of her three family members with a [0∶4] genotype had clinical symptoms. Eleven carrier couples had accepted prenatal diagnosis, and one fetus was found to have a [0∶4] genotype, and the pregnancy was terminated.@*CONCLUSION@#This study has determined the SMA carrier frequency in Dongguan region for the first time and provided prenatal diagnosis for carrier couples. The data can provide a reference for genetic counseling and prenatal diagnosis, which has important clinical implications for the prevention and control of birth defects associated with SMA.

Genetic mutation screening of glucose-6-phosphate dehydrogenase deficiency in Dongguan district / 中华医学遗传学杂志

OBJECTIVE@#To determine the incidence and genotypes of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Dongguan region of Guangdong Province and assess the efficacy and feasibility of flow-through hybridization.@*METHODS@#Peripheral blood samples were randomly selected and detected by modified G6PD/6PGD ratio method. Flow-through hybridization was used to detect 14 G6PD mutations among all samples.@*RESULTS@#In total 1005 samples were collected, the detection rate for modified G6PD/6PGD ratio method and flow-through hybridization were 2.79% and 20.90%, respectively. The consistency of the two methods was poor(Kappa=0.187). When c.1311C>T mutation is excluded, the consistency of the two methods was good for males (Kappa=0.952) but still poor for females (Kappa=0.194). The most common mutations were c.1376G>T, c.1388G>A and c.95A>G. No G6PD deficiency was found among those only carrying the c.1311C>T mutation.@*CONCLUSION@#Flow-through hybridization can simultaneously detect 14 loci, covering over 90% of common mutations in Chinese population, and can be easily expanded. The routine method may miss many females carrying homozygous, compound heterozygous and heterozygous mutations, but the detection rate for male hemizygous mutation was much higher.

Clinical application of semiconductor gene sequencing in screening thalassemia / 实用医学杂志

Objective To investigate the feasibility of semiconductor gene sequencing technology for thalassemia clinical screening and evaluate its application as compared with the results of PCR technology.Methods 197 visiting patients were randomly selected as prospective samples and200 patients ever diagnosed with thalassemia as previous samples.All the samples were detected by semiconductor technology gene sequencing and PCR technology at the same time and then evaluation of the advantage of semiconductor gene sequencing technology.Results 22 cases of 197 prospective samples were detected as thalassemia mutations by PCR technology,including 18 cases of α-thalassemia,3 cases of β-thalassemia,1 case of oα merge β thalassemia mutations.Semiconductor technology gene sequencing detected another 6 cases of rare type of thalassemia.By semiconductor gene sequencing technology on previous samples,118 cases of α-thalassemia,65 cases of β-thalassemia,17 case of α merge β thalassemia mutations,1 case of thalassemia mutations (HBA 1:c.223G ＞ C) were detected.By statistical analysis,the total coincidence rate of PCR technology and semiconductor gene sequencing was 98.5％,withthe Kappa =0.97(≥ 0.8).Conclusion Semiconductor gene sequencing technology for thalassemia clinical screening is feasible,for it can detect both thalassemia gene type,and new mutation.The results of semiconductor gene sequencing technology are accurate and the technology could be popularized in clinical application.

Analysis of the cause of pregnancy failure with combined MLPA assay for subtelomeric regions and ultrasonography / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the value of multiplex ligation-dependent probe amplification (MLPA) for the detection of chromosome abnormalities in miscarriage tissues, and to correlate the result with ultrasound findings.</p><p><b>METHODS</b>A total of 421 cases of spontaneous abortions and fetal deaths were detected with the MLPA method.</p><p><b>RESULTS</b>Among the 421 samples, 232 (55.11%) had an abnormal MLPA result. For the 286 cases derived from < 13 weeks pregnancy, 206 (72.03%) were abnormal. For the 49 cases from 14-19 weeks pregnancy, 14 (28.57%) were abnormal. For the 86 cases derived after 20 weeks pregnancy, 12 (13.95%) were abnormal. Among the 117 cases with abnormal ultrasound findings, 33 cases (28.21%) had an abnormal MLPA result, 28 out of the 33 cases were numerical chromosome abnormality, 4 cases were chromosome microdeletion and/or micro duplication, 1 case had both numerical abnormality and microduplication. For those with abnormal ultrasound findings for the neck region, fetal edematous syndrome, multiple malformations and digestive system, the detection rates for MLPA were 71.4%, 58.8%, 37.8%, and 9.1%, respectively. For those with abnormal finding of cardiac system, nervous system, face, skeletal system and urinary system, none was found with positive results of MLPA.</p><p><b>CONCLUSION</b>Numerical chromosomal abnormalities account for the majority of cases with spontaneous abortion. With the increase of gestational age, the occurrence of chromosomal abnormalities gradually declines. Combined ultrasound and MLPA assay can improve the detection rate and accuracy for chromosomal abormalities.</p>