OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for revealing the genetic etiology of fetuses with isolated ventricular septal defect (VSD). METHODS: From December 2017 to December 2020, 69 fetuses with isolated VSD were identified at the First Affiliated Hospital of Zhengzhou University. Meanwhile, 839 similar prenatal cases were selected from public databases including Wanfang data, Wanfang Medicine, and China National Knowledge Infrastructure (CNKI) by using keywords such as "Ventricular septal defect", "Copy number variation", and "Prenatal". A total of 908 fetuses with isolated VSD were analyzed. CNV-seq was carried out for 69 fetuses. RESULTS: Among the 908 fetuses, 33 (3.63%) were found to harbor pathogenic CNVs, which included 11 chromosomal aneuploidies (1.21%) and 22 pathogenic CNVs (2.42%). The pathogenic CNVs have involved 12 genetic syndromes, with those known to involve the heart development including 5 cases of 22q11.21 deletion syndrome, 2 cases of 4q terminal deletion syndrome, and 1 case of 9q subtelomere deletion syndrome. The outcome of pregnancies for 15 fetuses with pathogenic CNVs was known, of which 12 were terminated, and 3 had spontaneous closure of the ventricular septum after birth, but 1 of them had other abnormalities. CONCLUSION Fetuses with isolated VSD have a relatively high risk for chromosomal abnormalities, for which CNV-seq should be recommended.
Female ; Pregnancy ; Humans ; DNA Copy Number Variations ; Heart Septal Defects, Ventricular/genetics* ; 22q11 Deletion Syndrome ; Fetus

Objective:To investigate the relationship between parathyroid hormone（PTH） level and permanent hypoparathyroidism（PHPP） on the first day after radical papillary thyroidectomy, and its predictive value. Methods:A total of 80 patients with papillary thyroid cancer who underwent total thyroid resection and central lymph node dissection were collected and analyzed from January 2021 to January 2022. According to whether PHPP occurred after surgery, the patients were divided into hypoparathyroidism group and normal parathyroid function group, and univariate and binary logistics regression were used to analyze the correlation between PTH and serum calcium levels and PHPP on the first day after surgery in two groups. The dynamic changes of PTH at different time points after operation were analyzed. The area under the receiver operating characteristic was used to evaluate the predictive power of PTH on the development of PHPP after surgery. Results:Among the 80 patients with papillary thyroid cancer, 10 cases developed PHPP, with an incidence rate of 12.5%. Binary logistics regression analysis showed that PTH on the first postoperative day（OR=14.534, 95%CI: 2.377-88.858, P=0.004） was an independent predictive risk factor for postoperative PHPP. Taking PTH=8.75 ng/L on the first postoperative day as the cut-off value, the AUC of the area under the curve was 0.874（95%CI: 0.790-0.958, P<0.001）, the sensitivity was 71.4%, the specificity was 100%, and the Yoden index was 0.714. Conclusion:PTH level on the first day after total thyroid papillary carcinoma surgery is closely related to PHPP, and is an independent predictor of PHPP.
Humans ; Calcium ; Hypoparathyroidism/surgery* ; Parathyroid Glands ; Parathyroid Hormone ; Postoperative Complications/surgery* ; Thyroid Cancer, Papillary/surgery* ; Thyroid Neoplasms/complications* ; Thyroidectomy

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

Objective:To investigate the value of retrograde thyroidectomy from top to bottom in the operation of retrosternal thyroid surgery. Methods:Retrospective analysis was performed on the cases of retrosternal goiter excised by our surgeons from January 2017 to June 2022,the technical points, feasibility and advantages of the operation were summarized. Results:A total of 15 cases of retrosternal goiter treated by retrograde thyroidectomy were collected, including 5 cases of type Ⅰ retrosternal goiter and 10 cases of type Ⅱ retrosternal goiter.The postoperative pathology was benign. The surgical time is 40-60 minutes for unilateral retrosternal goiter and 70-90 minutes for bilateral goiter. All patients were discharged normally within 7 days after operation, and no operative complications were observed such as bleeding, hoarseness or hypoparathyroidism. Conclusion:This surgical excision method of thyroid is suitable for the type Ⅰ and type Ⅱ retrosternal goiter surgery, which can avoid the difficulties in exposing and separating the the inferior thyroid behind the sternum in conventional surgical method, speed up the operation and reduced the difficulty of operation, and has certain promotion value in clinic.
Humans ; Thyroidectomy/methods* ; Retrospective Studies ; Goiter, Substernal/pathology* ; Hypoparathyroidism/surgery*

Humans ; DiGeorge Syndrome/diagnostic imaging* ; Tetralogy of Fallot/surgery* ; Ultrasonography

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a male neonate featuring hypoparathyroidism, sensorineural hearing loss, and renal dysplasia (HDR) syndrome. METHODS: The child was subjected to genome-wide copy number variation (CNVs) analysis and whole exome sequencing (WES). Clinical data of the patient was analyzed. A literature review was also carried out. RESULTS: The patient, a male neonate, had presented with peculiar facial appearance, simian crease and sacrococcygeal mass. Blood test revealed hypocalcemia, hypoparathyroidism. Hearing test suggested bilateral sensorineural deafness. Doppler ultrasound showed absence of right kidney. Copy number variation sequencing revealed a 12.71 Mb deletion at 10p15.3-p13 (chr10: 105 001_12 815 001) region. WES confirmed haploinsufficiency of the GATA3 gene. With supplement of calcium and vitamin D, the condition of the child has improved. CONCLUSION The deletion of 10p15.3p13 probably underlay the HDR syndrome in this patient.
DNA Copy Number Variations ; Hearing Loss, Sensorineural/genetics* ; Humans ; Hypoparathyroidism/genetics* ; Infant, Newborn ; Kidney/abnormalities* ; Male ; Syndrome ; Urogenital Abnormalities/genetics*

OBJECTIVE: To analyze the prenatal ultrasonic characteristics and genetic features of 14 fetuses with chromosome 22q11 microdeletion syndrome (22q11DS). METHODS: 4989 fetuses were analyzed by using single nucleotide polymorphism array (SNP array) in the Fujian Maternal and Child Health Hospital from November 2016 to November 2019. RESULTS: SNP array showed that 11 fetuses had classic 3 Mb microdeletion in 22q11 region, one fetus had 2.0 Mb microdeletion, and two fetuses had 1.0 Mb microdeletion. The 1.0 Mb microdeletion in 22q11 region contains SNAP29 and CRKL genes, which may increase the risk of congenital renal malformation and cardiovascular malformation. CONCLUSION Prenatal ultrasonic characteristics of fetuses with 22q11 microdeletion syndrome vary, and SNP array is a powerful tool to diagnose such diseases, which can provide accurate genetic diagnosis and enable prenatal diagnosis.
22q11 Deletion Syndrome/diagnostic imaging* ; Chromosome Deletion ; Chromosomes, Human, Pair 22/genetics* ; Female ; Fetus ; Genetic Testing ; Humans ; Pregnancy ; Prenatal Diagnosis ; Ultrasonics

Repeated blood transfusions in transfusion dependent thalassemia (TDT) leads to iron overload-related endocrine complications. Hypoparathyroidism (HPT) with severe signs of hypocalcemia is a recognized complication among these patients. A 14-year-old thalassaemic boy, on regular transfusion and on anticonvulsant therapy with a presumptive diagnosis of epilepsy for the last 1 year, was admitted with high fever and severe muscle cramps with positive Trousseau’s sign. He was diagnosed as a case of primary HPT and magnesium deficiency on the basis of low serum calcium, high phosphate, normal alkaline phosphates, very low intact parathyroid hormone (iPTH), normal serum vitamin D and very low serum magnesium level. His calcium, magnesium and phosphate level normalised following treatment with intravenous magnesium and calcium. His iPTH improved but remained at low normal. He was discharged from hospital with oral calcium, calcitriol, and magnesium supplementation. The anticonvulsant (Phenobarbitone) was successfully withdrawn gradually over the next six months without any recurrence of seizure in the subsequent 3 years of follow up. Acquired HPT (apparently from hemosiderosis) is a common cause of hypocalcemia; and magnesium depletion further complicated the situation leading to severe hypocalcemia with recurrent episodes of convulsion. Magnesium replacement improved the parathyroid hormone (PTH) value proving its role in acquired HPT. Very high phosphate level on admission and poor PTH response with respect to the low serum calcium, indicates intrinsic parathyroid pathology. Metabolic abnormalities should always be evaluated in thalassaemic subject with seizure disorder and it appears that the initial convulsive episodes were due to hypocalcemia. Muscle pain, cramps or convulsion may occur from HPT and simultaneous magnesium deficiency in transfusion dependent thalassaemic subjects. Metabolic correction is more important than anticonvulsant medication. Calcium and magnesium should both be assessed routinely in transfusion dependent thalassemic patients.
Hemosiderosis ; Hypoparathyroidism ; Thalassemia

Aluminum (Al) is the third most abundant element in the earth's crust and is omnipresent in our environment, including our food. However, with normal renal function, oral and enteral ingestion of substances contaminated with Al, such as antacids and infant formulae, do not cause problems. The intestine, skin, and respiratory tract are barriers to Al entry into the blood. However, contamination of fluids given parenterally, such as parenteral nutrition solutions, or hemodialysis, peritoneal dialysis or even oral Al-containing substances to patients with impaired renal function could result in accumulation in bone, parathyroids, liver, spleen, and kidney. The toxic effects of Al to the skeleton include fractures accompanying a painful osteomalacia, hypoparathyroidism, microcytic anemia, cholestatic hepatotoxicity, and suppression of the renal enzyme 25-hydroxyvitamin D-1 alpha hydroxylase. The sources of Al include contamination of calcium and phosphate salts, albumin and heparin. Contamination occurs either from inability to remove the naturally accumulating Al or from leeching from glass columns used in compound purification processes. Awareness of this long-standing problem should allow physicians to choose pharmaceutical products with lower quantities of Al listed on the label as long as this practice is mandated by specific national drug regulatory agencies.
Aluminum ; Anemia ; Antacids ; Calcium ; Eating ; Glass ; Heparin ; Humans ; Hypoparathyroidism ; Infant Formula ; Intestines ; Kidney ; Leeching ; Liver ; Osteomalacia ; Parathyroid Glands ; Parenteral Nutrition Solutions ; Peritoneal Dialysis ; Pharmaceutical Preparations ; Renal Dialysis ; Respiratory System ; Salts ; Skeleton ; Skin ; Spleen

Fahr's disease (FD) is a rare neurologic disorder characterized by the symmetric and bilateral intracerebral calcification in a patient. We describe the case of a 65-year-old woman who presented with gait disturbance, abnormal mentality, and visual field defect. The result of a brain computerized tomography showed spontaneous intracranial hemorrhage in the right parieto-occipital area, and also showed the incidence of symmetric and bilateral intracerebral calcification. Moreover, laboratory studies indicated characteristic hypoparathyroidism. This brings us to understand that additionally, one of her sons also presented with similar intracerebral calcification, and was subsequently diagnosed with FD. Thus, her case was consistent with that of a patient experiencing FD. The patient had hypertension, which we now know might have caused the intracerebral hemorrhage. However, this patient's brain lesions were in uncommon locations for spontaneous intracerebral hemorrhage, and the lesions were noted as occurring away from the identified heavily calcified areas. Thus, it seemed that the massive calcification of cerebral vessels in the basal ganglia, the most common site of intracerebral hemorrhage, might have prevented a hypertensive intracerebral hemorrhage. Eventually, an intracerebral hemorrhage occurred in an uncommon location in the patient's brain.
Aged ; Basal Ganglia ; Brain ; Cerebral Hemorrhage ; Female ; Gait ; Humans ; Hypertension ; Hypoparathyroidism ; Incidence ; Intracranial Hemorrhage, Hypertensive ; Intracranial Hemorrhages ; Nervous System Diseases ; Visual Fields