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.

Two large novel alpha-globin gene cluster deletions causing alpha(0)-thalassemia in two Chinese families.

INTRODUCTION: Monosomy of terminal 16p13.3 is a relatively common subtelomeric abnormality, most affected individuals presented α-thalassemia, some also have mental retardation, developmental abnormalities and/or speech delay and facial dysmorphism, which is termed ATR-16 syndrome. Here, we reported two novel 16p13.3 deletions involving the α-globin gene cluster and multispecies conserved sequences (MCSs), causing only a phenotype of α-thalassemia. METHODS: Samples were collected from members of the two families and were subjected to haematological and comprehensive genetic analysis. RESULTS: The novel 108 Kb deletion in family A extends from the non-protein coding RNA gene (WASIR2) to the NPRL3 gene, removing MCS-R1 to R3. This deletion should arise de novo because it wasn't detected in both parents. The novel 336 Kb deletion in family B should extend from telomere to âˆ¼ chr16:336000, removing the entire α-globin gene cluster. Carriers of these two deletions presented with microcytosis and hypochromic red cells, in accordance with a phenotype of α0-thalassemia carrier. CONCLUSION: Our study increases the mutation spectrum of α-thalassemia. MCSs deletion should be considered in clinical practice of thalassemia screening and diagnosis.

Hyperhaemolysis in a pregnant woman with a homozygous ß0 -thalassemia mutation and two genetic modifiers.

INTRODUCTION: Patients with a homozygous ß0 -thalassemia mutation usually have a transfusion-dependent ß-thalassemia major phenotype. However, some ß-thalassemia patients present with a relatively mild and even normal phenotype and always have a high level of Hb F induced by genetic modifiers. METHODS: In this study, we identified a homozygous ß0 -thalassemia mutation (HBB: c.126_129delCTTT) in a 36-year-old pregnant woman. She had not presented any clinical symptoms of ß-thalassemia since birth. To investigate her unexpected mild phenotype, known genetic modifiers that ameliorate the severity of ß-thalassemia were analysed. Besides, we described the haematological changes during pregnancy. RESULTS: Two genetic modifiers (a heterozygous KLF1: c.519_525dup mutation; and two homozygous HBS1L-MYB locus SNP variants: rs7776054 and rs9399137) were identified. However, she showed a gradually decreased level of Hb during pregnancy, and serious transfusion complication of hyperhaemolysis was induced and complicated the pregnancy. CONCLUSION: This report is in accordance with previous findings that genetic modifiers can ameliorate the clinical severity of ß-thalassemia, even without obvious clinical symptoms in a prolonged steady state. However, the steady state can be disrupted during pregnancy. In addition, raising awareness of hyperhaemolysis among clinicians treating patients with thalassemia is necessary.

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>

Analysis of related factors of bleeding of uterine scar again after cesarean section / 中国基层医药

Objective To study the related factors of hemorrhage of uterine scar again after cesarean section,available for peer exchange.Methods A retrospective analysis of clinical data of 650 patients with scar uterus again cesarean section patients,analysis of postoperative hemorrhage patients,the causes of bleeding.They were divided into placental group (n =6),incision dehiscence group (n =7),uterine atony group (n =17)according to the causes of hemorrhage,and related factors of postoperative bleeding were analyzed.Results The bleeding volume of the placental group in operation[(2 500 ±500)mL]was higher than the uterine atony group[(1 300 ±400)mL] and the incision dehiscence group[(700 ±200)mL].The bleeding volume of the uterine atony group was higher than the incision dehiscence group (t =10.29,5.56,4.33,all P <0.05).The bleeding volume of the uterine atony group after operation[(100.09 ±36.45)mL]was higher than the placental group[(90.71 ±20.31)mL]and the uterine atony group[(81.23 ±30.34)mL].The bleeding volume of the placental group after operation were higher than the uterine atony group (t =3.94,3.02,2.78,all P <0.05).4 cases of hysterectomy,3 cases of conservative surgery in placental group.1 case of hysterectomy,16 cases of conservative surgery in uterine atony group.7 cases conservative surgery in incision dehiscence group.Conclusion placental factors,uterine atony,incision dehiscence all can lead to scar uterus again cesarean section hemorrhage.We should also strengthen the clinical prevention work,and actively take relevant measures,reduce postoperative bleeding risk,to ensure the safety of the mother and infant.