DiGeorge Syndrome ; genetics ; Humans ; Phenotype ; Twins, Monozygotic

Chromosomes, Human, Pair 22 ; genetics ; DiGeorge Syndrome ; genetics ; Humans ; Mutation ; Schizophrenia ; etiology ; genetics

We report a 32 year-old Chinese lady with history of tetralogy of Fallot, presented to us with chest pain due to hypocalcemia secondary to hypoparathyroidism. With her dysmorphic facial features and intellectual disability 22q11.2 deletion was suspected and confirmed by genetic study. Clinicians should consider the diagnosis of DiGeorge syndrome in adult patient with past medical history of congenital heart disease, facial dysmorphism, intellectual disability and primary hypoparathyroidism.
Adult ; Delayed Diagnosis ; DiGeorge Syndrome ; diagnosis ; genetics ; Female ; Humans ; Hypocalcemia ; diagnosis ; genetics

OBJECTIVE: To explore the cause for a twin pregnancy with false negative result for 22q11.2 deletion syndrome by expanded non-invasive prenatal testing (NIPT-plus). METHODS: A pregnant woman with twin pregnancy through in-vitro fertilization and negative result of NIPT-plus was selected as the study subject. Amniocentesis was conducted after ultrasonic finding of fetal abnormalities. In addition to conventional G-banded karyotyping, copy number variation sequencing (CNV-Seq) was used to detect chromosomal microdeletion and microduplication. Clinical data of the woman were analyzed to explore the reasons underlying the false negative result. RESULTS: NIPT-plus has yielded a negative result with 11.77 Mb unique reads and 3.05% fetal fraction. Both fetuses had a normal karyotype (46,XY and 46,XX). CNV-seq indicated that one of the fetuses was normal, whilst the other was diagnosed with a 2.58 Mb deletion in the 22q11.2 region. CONCLUSION The false negative result may be attributed to the combined influence of low fetal fraction, high BMI, twin pregnancy through IVF and a relatively small deletion fragment. Ultrasonography exam following a low-risk result of NIPT-plus should not be neglected.
Pregnancy ; Female ; Humans ; Prenatal Diagnosis ; Pregnancy, Twin/genetics* ; DiGeorge Syndrome/genetics* ; DNA Copy Number Variations ; Amniocentesis

Chromosome Deletion ; Chromosomes, Human, Pair 22 ; DiGeorge Syndrome ; diagnosis ; genetics ; Humans ; Infant ; Male

OBJECTIVE: To investigate the relationship between 22q11.2 duplication and clinical phenotype. METHODS: Eight fetuses with 22q11.2 duplication syndrome diagnosed by chromosome microarray analysis (CMA) through amniocentesis from February 2015 to March 2017 were enrolled in the study. The prenatal diagnostic indications, fetal ultrasound, chromosome karyotype, peripheral blood CMA results of parents, pregnancy outcomes and follow-up of postnatal growth and development were retrospectively analyzed. RESULTS: Prenatal serological screening indicated 6 cases with high risk of trisomy 21, 1 case with nuchal fold (NF) thickening and 1 case of maternal chromosomal balanced translocation. Fetal ultrasonography showed 1 case of NF thickening, 1 case of fetal cerebral ventriculomegaly and 6 cases with normal ultrasound. CMA demonstrated that the size of duplication was between 651 kb and 3.26 Mb, and 22q11.2 duplication. Parents' CMA results revealed that 6 cases inherited from one of the parents with normal phenotype, and the parents of 2 cases refused the CMA test. Two couples chose induced labor; 6 cases of continued pregnancy had normal phenotypes at birth. All 6 cases were followed up with longest of 3.5 years. The growth and psychological development were normal in 5 cases, and one case was growth retardation. CONCLUSIONS There were no specific clinical phenotypes in 22q11.2 duplication syndrome, and most of them were inherited from one parent who has normal phenotype.
Abnormalities, Multiple ; diagnosis ; genetics ; Chromosome Duplication ; genetics ; Chromosomes, Human, Pair 22 ; genetics ; DiGeorge Syndrome ; diagnosis ; genetics ; Female ; Humans ; Male ; Pregnancy ; Pregnancy Outcome ; Prenatal Diagnosis ; Retrospective Studies

OBJECTIVETo establish a method for the prenatal diagnosis of 22q11 microdeletion syndrome.

METHODSBACs-on-Beads (BoBs) and fluorescence in situ hybridization (FISH) were performed on a fetus for whom amniotic chromosomal culturing has failed and a pair of twin fetuses suspected for 22q11 deletion syndrome.

RESULTS22q11 microdeletion was detected in all 3 fetuses by prenatal BoBs as well as FISH, with only one red signal detected at the DiGeorge/VCFS N25 site and two green signals on the 22q13.3 ARSA site.

CONCLUSIONThe combination of prenatal BoBs and FISH can provide a method for the prenatal diagnosis of 22q11 microdeletion.

Adult ; Chromosome Deletion ; Chromosomes, Human, Pair 22 ; genetics ; DiGeorge Syndrome ; diagnosis ; embryology ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Pregnancy ; Prenatal Diagnosis

BACKGROUND: Microdeletion syndromes not detectable by conventional cytogenetic analysis have been reported to occur in approximately 5% of patients with unexplained mental retardation (MR). Therefore, it is essential to ensure that patients with MR are screened for these microdeletion syndromes. Mental retardation syndrome multiplex ligation-dependent probe amplification (MRS-MLPA) is a new technique for measuring sequence dosages that allows for the detection of copy number changes of several microdeletion syndromes (1p36 deletion syndrome, Williams syndrome, Smith-Magenis syndrome, Miller-Dieker syndrome, DiGeorge syndrome, Prader-Willi/Angelman syndrome, Alagille syndrome, Saethre-Chotzen syndrome, and Sotos syndrome) to be processed simultaneously, thus significantly reducing the amount of laboratory work. METHODS: We assessed the performance of MLPA (MRC-Holland, The Netherlands) for the detection of microdeletion syndromes by comparing the results with those generated using FISH assays. MLPA analysis was carried out on 12 patients with microdeletion confirmed by FISH (three DiGeorge syndrome, four Williams syndrome, four Prader-Willi syndrome, and one Miller-Dieker syndrome). RESULTS: The results of MLPA analysis showed a complete concordance with FISH in 12 patients with microdeletion syndromes. CONCLUSIONS: On the basis of these results, we conclude that MLPA is an accurate, reliable, and cost-effective alternative to FISH in the screening for microdeletion syndromes.
*Chromosome Deletion ; Classical Lissencephalies and Subcortical Band Heterotopias/genetics ; DiGeorge Syndrome/genetics ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Laboratories, Hospital ; Mental Retardation/*diagnosis/genetics ; Nucleic Acid Amplification Techniques/*methods ; Prader-Willi Syndrome/genetics ; Williams Syndrome/genetics

OBJECTIVETo investigate clinical features and the diagnosis by fluorescence in situ hybridization (FISH) of 22q11 microdeletion syndrome (22q11 DS).

METHODSThe clinical data of suspects were analyzed, and their peripheral blood samples were tested by FISH for microdeletion of 22q11. The diagnosis and correlated clinical factors of 22q11 DS were investigated by using the multiple factor Logistic regression analysis and Chi-square test.

RESULTSIn 64 suspects, 14 were shown to have 22q11 microdeletion with many different types of malformation, and the percentage was 21.9%. The Logistic regression predictive equation for 22q11 DS was: y=-8.206+2.324x1+2.725x2+1.674x3, P=exp(y)/[1+exp(y)], in which the concomit ant variables were facial dysmorphic features (x1), congenital heart defects (x2), thymus scarcity/infection problem (x3), the P value meant the probability of diagnosis of 22q11 DS.

CONCLUSIONAccurate clinical evaluation is just as preliminary screening to patients at risk for del22q11. The results of FISH test can be predicted by using the suitable Logistic regression equation.

Adolescent ; Adult ; Child ; Child, Preschool ; Chromosome Deletion ; Chromosomes, Human, Pair 22 ; genetics ; DiGeorge Syndrome ; diagnosis ; genetics ; pathology ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Logistic Models ; Male

OBJECTIVETo carry out genetic analysis for two patients affected with congenital heart disease, developmental delay with or without cleft palate.

METHODSCytogenetic and molecular genetic methods including karyotyping, fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and single nucleotide polymorphisms array (SNP-array) were employed to detect potential mutations. For parents of both patients, MLPA was used to analyze whether they were carrier of the deletion.

RESULTSFor neither patient, no abnormality was detected upon karyotype analysis. However, FISH analysis has indicated the presence of 22q11.2 deletion. SNP-array analysis has confirmed that both patients have carried a 2.5 Mb deletion in the 22q11.2 region. MLPA analysis suggested none of the parents has carried the same deletion.

CONCLUSIONAlthough the phenotypes of our patients were not identical, they were both diagnosed as 22q11.2 deletion syndrome by multiple methods. The deletions in both cases were de novo in nature. Precise delineation of the genotype can facilitate better understanding of the patients' phenotype.

Abnormalities, Multiple ; genetics ; pathology ; Child, Preschool ; Chromosome Deletion ; Chromosomes, Human, Pair 22 ; genetics ; DiGeorge Syndrome ; genetics ; pathology ; Ear, External ; abnormalities ; Genotype ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Karyotyping ; Male ; Microarray Analysis ; methods ; Phenotype ; Polymorphism, Single Nucleotide ; Syndrome