Carrier screening and prenatal diagnosis for thalassemia-associated mutations in Jiaxing area of Zhejiang / 中华医学遗传学杂志

OBJECTIVE@#To study the molecular epidemiology of thalassemia in Jiaxing area of Zhejiang province and provide a basis for prenatal diagnosis, genetic counseling and prevention and control of birth defects.@*METHODS@#A total of 24 003 pregnant women who presented at the Jiaxing Maternal and Child Health Care Hospital from April 2017 to September 2021 were enrolled. Capillary hemoglobin electrophoresis in combination with routine blood test were used for primary screening for carriers of thalassemia-associated mutations, and those with positive results were subjected to fluorescence quantitative PCR assay. Prenatal diagnosis was provided for couples with a risk of giving birth to children with intermediate or severe thalassemia.@*RESULTS@#Among the 24 003 pregnant women, 1 211 cases were suspected as carriers of thalassemia-associated mutations, among whom 443 (36.58%) were confirmed by genetic testing. Among these, carriers of α-, β- and α-complex β-globin gene mutations have accounted for 27.31% (121/443), 70.65% (313/443) and 2.04% (9/443), respectively. The result of prenatal diagnosis for an at-risk couple was --SEA/αCSα, and the fetus was predicted to have intermediate or severe thalassemia. Termination of the pregnancy was recommended.@*CONCLUSION@#Hemoglobin electrophoresis combined with routine blood test during pregnancy may be used as a preliminary screening measure for carriers of thalassemia-associated variants. Combined with genetic testing, this will be of great significance for the control of thalassemia in this region.

Incidence and genetic reproductive characteristics of AZFc microdeletion among patients with azoospermia or severe oligospermia / 中华医学遗传学杂志

OBJECTIVE@#To explore the incidence of azoospermia factor c (AZFc) microdeletion among patients with azoospermia or severe oligospermia, its association with sex hormone/chromosomal karyotype, and its effect on the outcome of pregnancy following intracytoplasmic sperm injection (ICSI) treatment.@*METHODS@#A total of 1 364 males with azoospermia or severe oligospermia who presented at the Affiliated Maternity and Child Health Care Hospital of Jiaxing College between 2013 and 2020 were subjected to AZF microdeletion and chromosome karyotyping analysis. The level of reproductive hormones in patients with AZFc deletions was compared with those of control groups A (with normal sperm indices) and B (azoospermia or severe oligospermia without AZFc microdeletion). The outcome of pregnancies for the AZFc-ICSI couples was compared with that of the control groups in regard to fertilization rate, superior embryo rate and clinical pregnancy rate.@*RESULTS@#A total of 51 patients were found to harbor AZFc microdeletion, which yielded a detection rate of 3.74%. Seven patients also had chromosomal aberrations. Compared with control group A, patients with AZFc deletion had higher levels of PRL, FSH and LH (P < 0.05), whilst compared with control group B, only the PRL and FSH were increased (P < 0.05). Twenty two AZFc couples underwent ICSI treatment, and no significant difference was found in the rate of superior embryos and clinical pregnancy between the AZFc-ICSI couples and the control group (P > 0.05).@*CONCLUSION@#The incidence of AZFc microdeletion was 3.74% among patients with azoospermia or severe oligospermia. AZFc microdeletion was associated with chromosomal aberrations and increased levels of PRL, FSH and LH, but did not affect the clinical pregnancy rate after ICSI treatment.

Application of non-invasive prenatal testing for the screening of fetal chromosomal abnormalities in 12 085 cases / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of non-invasive prenatal testing (NIPT) for the screening of fetal chromosomal abnormalities.@*METHODS@#For 12 085 pregnant women, the results of NIPT and invasive prenatal diagnosis were compared.@*RESULTS@#The test was successful in 12 067 cases and has detected 179 chromosomal abnormalities, with a positive rate of 1.48%, sensitivity of 98.39% and specificity of 99.02%. Invasive prenatal diagnosis was performed for 3 of 18 patients who had failed NIPT but has detected no karyotypic abnormality. Except for one case of twin Cesarean section which delivered a normal female fetus and a stillbirth of unknown sex, the remainder of the 18 cases all had a normal delivery. The positive rate of NIPT screening for the abnormal ultrasound group was significant higher than that other groups (P< 0.01). Among those with positive results of NIPT, 122 underwent invasive prenatal diagnosis, and 25 trisomy 21, 7 trisomy 18, 3 trisomy 13, 4 aneuploidies of other autosomes, 13 sex chromosomal aneuploidies and 9 microdeletion/microduplications were confirmed, which yielded a positive predictive rate of 86.21%, 50.00%, 23.08%, 21.05%, 46.43%, and 47.36%, respectively.@*CONCLUSION@#NIPT has high sensitivity, specificity and positive predictive value, and is an effective method for prenatal screening. In addition to chromosomes 21, 18 and 13, NIPT has certain predictive value for other autosomal aneuploidies, sex chromosomal aneuploidies, microdeletion/microduplications, and can provide a reference for karyotype analysis and chromosomal microarray verification.

Prenatal diagnosis of a novel SOX10 mutation in a patient with syndromic hearing loss / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a patient with syndromic hearing loss.@*METHODS@#Genomic DNA of the patient was extracted, for which 127 deafness-related genes were enriched with a chip. Following next generation sequencing, pathogenic loci in exonic regions were analyzed through comparison against the databases. Genotype of her fetus for the suspected site was determined by testing the amniotic fluid sample. qPCR method was applied to verify the deletion of a large fragment.@*RESULTS@#The proband was diagnosed with Waardenburg syndrome type 2, and had harbored a novel heterozygous deletion of the exons 3 and 4 of the SOX10 gene. Her fetus was found to carry the same deletion and presented with blue eyes and deafness after birth.@*CONCLUSION@#Waardenburg syndrome type 2 due to SOX10 gene deletion may feature autosomal dominant inheritance with incomplete penetrance. The deletion of exons 3 and 4 of the SOX10 gene probably underlies the disease in this family.

Diagnosis and reproductive guidance for a couple carrying a novel c.1893C>T mutation of the TECTA gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the molecular basis for an individual with postnatal deafness and provide genetic counseling for her family.@*METHODS@#Following extraction of genomic DNA from peripheral blood samples, 127 genes associated with deafness were subjected to targeted capturing and next generation sequencing. Suspected mutation was verified by Sanger sequencing.@*RESULTS@#The proband was found to carry a homozygous c.1893C>A mutation in the TECTA gene, which is located in the tectorial membrane of inner ear and may cause premature termination of translation of TECTA protein. In addition, two heterozygous mutations, c.13010C>T and c.12790G>A, were found in the USH2A gene. Whilst the former is likely to be pathogenic, the latter has unknown clinical significance. Further analysis suggested that all three mutations have derived from the parents of the proband.@*CONCLUSION@#The homozygous c.1893C>A mutation of the TECTA gene probably underlies the proband's hearing loss which conformed to an autosomal recessive inheritance.

A case of Wolf-Hirschhorn syndrome diagnosed by single nucleotide polymorphism array / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genetic causes for a child with multiple congenital malformations and epilepsy through analysis of copy number variations, and to correlate the genotype with the phenotype.</p><p><b>METHODS</b>G-banding karyotyping was performed on the child and her parents. Single nucleotide polymorphisms array (SNP-array) was used to map the exact chromosomal breakpoints in the proband. The result was validated with fluorescence in situ hybridization (FISH).</p><p><b>RESULTS</b>G banding analysis suggested that the proband had a karyotype of 46,XX,del(4)(p15), while both of his parents had a normal karyotype. SNP-array has identified a hemizygous deletion of 13.3 Mb on chromosome 4p16.3p15.33, which has been implicated in Wolf-Hirschhorn syndrome. FISH assay has confirmed the de novo origin of the deletion, with the karyotype and clinical phenotype of both parents taken into consideration.</p><p><b>CONCLUSION</b>A case of Wolf-Hirschhorn syndrome has been diagnosed by clinical manifestation and karyotyping analysis. Compared with conventional karyotyping analysis, SNP-array has greater resolution and accuracy, and can provide useful information for genetic counseling.</p>

Diagnosis of a case with Williams-Beuren syndrome by single nucleotide polymorphism array / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genetic cause for a child with mental retardation, developmental delay and multi-systemic developmental disorders by analyzing the copy number variations (CNVs) and correlating the genotype with the phenotype.</p><p><b>METHODS</b>Routine G-banding was performed to analyze the karyotype of the patient and her parents. In addition, single nucleotide polymorphisms array (SNP-array) was used to determine the CNVs, which was confirmed by fluorescence in situ hybridization (FISH).</p><p><b>RESULTS</b>No karyotypic abnormality was detected upon chromosome analysis. However, SNP-array has identified a de novo hemizygous deletion of 1673 kb on chromosome region 7q11.23, which has been associated with Williams-Beuren syndrome. The microdeletion was confirmed by FISH testing.</p><p><b>CONCLUSION</b>A child with Williams-Beuren syndrome has been diagnosed by SNP-array and FISH. The de novo 7q11.23 microdeletion probably underlies the clinical manifestation of the patient. Compared with routine karyotype analysis, SNP-array is more useful for diagnosing children with multiple congenital anomalies with unclear etiology.</p>