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Objective: To explore the genetic etiology for a child featuring mental retardation, language delay and autism., Methods: G-banding chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) were carried out for the child and her parents., Results: The child was found to have a 46,XX,dup(8p?) karyotype, for which both of her parents were normal. SNP-array revealed that the child has harbored a 6.8 Mb deletion in 8p23.3p23.1 and a 21.8 Mb duplication in 8p23.1p12, both of which were verified as de novo pathogenic copy number variants., Conclusion: The clinical features of the child may be attributed to the 8p deletion and duplication. SNP-array can facilitate genetic diagnosis for children featuring mental retardation in conjunct with other developmental anomalies.

Objective: To explore the genetic etiology for a patient featuring intellectual disability and torticollis., Methods: Peripheral blood sample was collected from the patient and subjected to G-banded karyotyping analysis and single nucleotide polymorphism array (SNP-array) assay., Results: The patient was found to have a chromosomal karyotype of 46,XX. SNP-array revealed that she has harbored a 3.8 Mb microdeletion at 10q26.3 which has encompassed 21 OMIM genes including EBF3 and ECHS1, and a 7.3 Mb duplication at 18q22.3q23 which has encompassed 19 OMIM genes including TSHZ1 and TXNL4A. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the 10q26.3 deletion was predicted to be pathogenic, whilst the 18q22.3q23 duplication was predicted to be variation of unknown significance., Conclusion: The clinical phenotype of the patient may be mainly attributed to the 10q26.3 microdeletion, and haploinsufficiency of the EBF3 gene may account for her intellectual deficiency. Above finding has provided a basis for genetic counseling for the patient.

Objective: To delineate a small supernumerary marker chromosome (sSMC) derived from chromosome 9 with combined cytogenetic and molecular methods., Methods: For a pregnant woman with fetal ultrasound revealing left ventricular punctate hyperechoic echo, and a high risk for monosomy or partial deletion of chromosome 8, chromosome 9 trisomy, monosomy or partial deletion of chromosome 11 by non-invasive prenatal testing, and an abnormal MOM value revealed by mid-term serum screening, amniocentesis was performed for G banded chromosomal analysis and single nucleotide polymorphism array (SNP-array) assay. Peripheral blood samples of the woman and her spouse were also collected for the above tests. In addition, the woman was further subjected to C banding karyotyping analysis and fluorescence in situ hybridization (FISH) assay., Results: The G-banded karyotype of the pregnant women was 47,XX,+mar[20]/46,XX[80], whilst C-banding analysis showed a deep stain in the middle of the sSMC (suggestive of centromeric region) and light stain at both ends (suggestive of euchromatism). FISH combined with DAPI banding analysis using 9pter/9qter probes revealed a karyotype of 47,XX,+mar.ish i(9)(9p10)(9p++)[2]/46,XX[18], whilst SNP-array has revealed a 68.1 Mb duplication in the 9p24.3q13 region. A database search has suggested the duplication to be likely pathogenic. No abnormality was found in her fetus and spouse by karyotyping and SNP-array analysis., Conclusion: Through combined cytogenetic and molecular genetic analysis, a sSMC derived from chromosome 9 was delineated, which has enabled genetic counseling for the couple.

Objective: To explore the genetic etiology of spontaneous abortions by using chromosomal microarray analysis (CMA)., Methods: Fetal tissues derived from 106 spontaneous abortion samples were subjected to CMA assay to detect genome copy number variants (CNVs)., Results: The test was successful in 94 cases (88.68%). Fifty four chromosomal abnormalities were detected, which included 44 numerical chromosomal aberrations mainly consisting of aneuploidies, triploidies and mosaicisms. Four pathogenic CNVs were detected, and two of which involved the Cri-du-chat syndrome regions. In addition, 6 chromosomal mosaicism were detected., Conclusion: Numerical chromosomal aberrations and CNVs are the main causes for early spontaneous abortions. CMA can effectively reveal the genetic etiology of spontaneous abortions. Spontaneous abortions at gestational weeks 10 to 11 +6 has the highest rate for chromosomal abnormalities, which may provide valuable information for clinical counseling.

Objective: To assess the application value of combined detection of HbA2 and HbF for the screening of thalassemia among a population of childbearing age in Quanzhou, Fujian, and determine the optimal cut-off values for the region., Methods: Capillary hemoglobin electrophoresis and genetic testing for α and β globin gene mutations were simultaneously carried out on 11 428 patients with suspected thalassemia. Statistical methods were used to analyze the distribution of various types of thalassemia and compare the performance of HbA2 and HbF measurement for the screening of various types of thalassemia. The optimal cut-off values for HbA2 and HbF were determined with the ROC curves., Results: 4591 patients with α, β, and αβ compound thalassemia were identified by genetic testing. The most common genotypes for α and β thalassemia included --SEA/αα and β654/βN, β41-42/βN, and β17/βN. The ROC curves were drawn to compare the performance of HbA2 screening for α-, β-, αβ-compound, static α-, mild α-, and intermediate α-thalassemia, and the maximum area under the curves was 0.674, 0.984, 0.936, 0.499, 0.731, 0.956, and the optimal cut-off values for HbA2 were 2.45%, 3.25%, 3.65%, 2.95%, 2.55%, 1.75%, respectively., Conclusion: HbA2 is an efficient indicator for identifying intermediate types of α-, β-, and αβ compound thalassemia. The combination of HbA2 and HbF measurement can effectively detect carriers for β-thalassemia mutations.

Objective: To explore the genetic etiology of a neonate with suggestive features of Cornelia de Lange Syndrome (CdLS)., Methods: Chromosome karyotyping, copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the child. Meanwhile, peripheral venous blood samples were taken from his parents for verifying the suspected pathogenic variants detected in the child., Results: The child has exhibited developmental delay, microcephaly, ptosis, micrognathia, and low ear setting, and was suspected as CdLS. No abnormality was found by karyotyping and CNV-seq analysis. WES has detected 5 heterogeneous variants and 1 hemizygous variant on the X chromosome. Combining the genetic pattern and result of family verification, a hemizygous C.3500T>C (p.ile1167thr) of the SMC1A gene was predicted to underlay the clinical manifestations of the patient. This variant was not recorded in the dbSNP and gnomAD database. PolyPhen2, Provean, SIFT all predicted the variant to be harmful, and PhastCons conservative prediction is was a conservative mutation. ACMG variant classification standard evidence supports are PM2, PP2, and PP3., Conclusion: The novel c.3500T>C (p.Ile1167Thr) missense mutation of the SMC1A gene probably underlay the genetic etiology of CdLS in this child. Above results has enriched the mutation spectrum of CdLS type II, and facilitated clinical counseling for this family.

Objective: To apply combined non-invasive prenatal testing (NIPT), chromosomal karyotyping and chromosomal microarray for the screening and prenatal diagnosis of a fetus with supernumerary small marker chromosome (sSMC)., Methods: Standard NIFTY and full gene NIFTY kits were applied to detect free DNA (cfDNA) isolated from peripheral blood sample of a pregnancy woman. Amniocentesis was carried out for the woman for an abnormal NIPT result. G-banded karyotyping and single nucleotide polymorphism array (SNP array) were used to determine the karyotype and copy number variants in the fetus. The result was validated with a fluorescence in situ hybridization (FISH) assay., Results: Both the standard NIFTY and full gene NIFTY indicated abnormal dup(chr12:707 334-33 308 759), for which the T score value of copy number anomaly in full gene NIFTY is 6.823, which is higher than the standard NIFTY's T-score value of 3.9535. The two NIFTY results were both above the normal threshold ± 3. Conventional G-banding analysis of amniocytes showed that the fetus has a karyotype of 47,XY,+mar. SNP-array delineated duplication of 12p (arr [hg19]12p13.33p11.1 (173 786_34 385 641)× 4, which was verified by FISH. Based on the above results, the fetus was diagnosed as a novel case of Pallister-Killian syndrome., Conclusion: NIPT has a certain value for the prenatal detection of PKS. Combined use of multiple techniques can facilitate delineation of the source of sSMC.

Objective: To explore the genetic basis for a child featuring developmental delay, intelligent disability and language deficit., Methods: Peripheral blood samples of the child and her parents were collected for routine G-banding karyotyping analysis and single nucleotide polymorphism array (SNP array) detection. Amniotic fluid was also sampled from the mother for karyotyping analysis and SNP array detection., Results: No karyotypic abnormality was found with the child and her parents. SNP array showed that the child has carried a 761.4 kb microdeletion at 16p11.2, while her mother has carried a 444.4 kb microduplication at 15q13.3. Her father's result was negative. Further analysis showed that the 15q13.3 microduplication was inherited from her maternal grandfather who was phenotypically normal. Prenatal diagnosis showed that the fetus has inherited the15q13.3 microduplication from its mother., Conclusion: The child has carried a de novo 16p11.2 microdeletion, which overlaps with 16p11.2 microdeletion syndrome region, in addition with similar clinical phenotypes. The 16p11.2 microdeletion probably underlies her abnormal phenotype.

Objective: To explore the genetic basis of a child with developmental delay and intellectual disability., Methods: Peripheral blood samples of the child and his parents were collected for routine G-band karyotyping analysis and single nucleotide polymorphism array (SNP array) assay. Amniotic fluid sample was collected during the next pregnancy for prenatal diagnosis., Results: No karyotypic abnormality was found in the child and his parents. SNP array showed that the child has carried a 855.3 kb microduplication in 15q11.2. His mother carried the same duplication but had no phenotypic anomaly. No microdeletion/microduplication was found in his father. Upon prenatal diagnosis, no abnormalities was found with the chromosomal karyotype and SNP array result of the fetus., Conclusion: 15q11.2 microduplication may result in developmental delay and intellectual disability, for which CYFIP1 may be a candidate gene. However, the duplication may increase the risk but with a low penetrance. This should attract attention during clinical consultation.

Objective: To analyze partial deletion of the long arm of X chromosome in a family and explore the mechanism underlying its phenotypes., Methods: G-banding technique was employed to analyze the karyotypes of the subjects, and fluorescence in situ hybridization (FISH) was used to analyze their X chromosomes with Xpter, Xqter and WCPX probes., Results: The karyotypes of the proband, her mother and her fetus were all 46,X,del(X)(q24). Combined FISH and karyotyping analysis suggested that the proband and her fetus both carried a Xq24q27.3 deletion., Conclusion: The Xq24q27.3 deletion carried by the family is closely related with premature ovarian failure but not with short stature, gonadal dysgenesis and primary amenorrhea.