Objective:To analyze the clinical features and CYP17A1 gene mutation of 17α-hydroxylase/17, 20-lyase deficiency (17OHD). Methods:The clinical data, laboratory examination and genetic results of 6 children with 17OHD in the Department of Endocrinology, Children′s Hospital Affiliated to Capital Institute of Pediatrics from March 2014 to December 2019 were enrolled and analyzed retrospectively.Meanwhile, the clinical types of all congenital adrenocortical hyperplasia (CAH) patients were calculated and then the incidence of 17OHD was calculated.Results:The 6 cases were from 5 families, and the age at diagnosis was ranged from 1 year and 6 months to 15 years old, in which 2 cases were 46, XX and 4 cases were 46, XY.Their gender were all female.Three cases presented with hypertension (50.0%), 4 cases with hypokalemia (66.7%), and 1 case with labia mass (16.7%). The gonad developed into a testis in patients with 46, XY, and patients with 46, XX had ovarian hypoplasia.The laboratory tests revealed an decrease in the cortisol at 8 AM in all cases, ranging from 0.62 to 5.93 mg/L.Five cases displayed an increase in adrenocorticotropic hormone (ACTH) in the range of 84-271 ng/L, and 1 patient with normal ACTH (58 ng/L) had a peak cortisol of 1.75 mg/L after the ACTH challenge test.Elevated progesterone was detected in 6 patients with a normal 17 hydroxyprogesterone level.Further results proved low levels of testosterone and estradiol, and high levels of luteinizing hormone (LH), and follicle stimulating hormone (FSH). CT scan showed mild adrenal hyperplasia in all cases.Among 114 CAH patients during the same period, the incidence of 17OHD came second at 5.3%.The CYP17A1 gene mutation results indicated that 2 unrelated patients were homozygous mutation for p. Y329fs (c.985_987delTACinsAA), 2 siblings were compound heterozygous mutations for p. Y329fs and exon 1-7 deletion, 1 patient was compound heterozygous mutations of p. Y329fs and p. R416C (c.1246C>T), and 1 patient was homozygous mutations for p. L465P (c.1394T> C), which was first reported in China. Conclusions:17OHD is not rare in CAH.Female children with hypokalemia, hypertension, and hypogonadism can lead to diagnostic suspicion of 17OHD.The p. Y329fs mutation in Chinese 17OHD children is a hotspot.The p. L465P (c.1394T>C) mutation is a new mutation in China and it could enrich the mutant spectrum of CYP17A1 gene in China.

Pituitary stalk interruption syndrome (PSIS) is characterized by a thin or absent pituitary stalk,hypoplasia of the adenohypophysis,and ectopic neurohypophysis.PSIS manifestations include a wide spectrum of clinical phenotypes and pituitary hormone deficiencies of variable degree and timing of onset.To date,the underlying mechanisms involved in PSIS ontogenesis have remained unclear.Perinatal injury and abnormal pituitary development during the embryonic period have more recently been proposed.Thus far,10 genes mutations,chromosome micro deletions and micro duplications are proved to have been associated with PSIS.Now,the research advances of etiology of PSIS ave reviewed.

Objective: To investigate the clinical features and genetic characteristics of patients with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene variants. Method: The clinical data of a patient with ENPP1 homozygous variants from Capital Institute of Pediatrics was collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and PubMed by using search term "ENPP1" , "hypophosphatemic rickets" . The literature retrieval was confined from 1980 to February 2017. The clinical manifestations, bone metabolism examinations, X-RAY and genotypes were reviewed. Result: Our patient was an 11 years old girl, with 7 years history of lower limb malformation. She showed significant valgus deformity of the knee (genu valgum). Metabolic examination revealed reduced level of plasma phosphate (0.86 mmol/L), a normal level of plasma calcium (2.30 mmol/L) and an elevated alkaline phosphatase level of 688 IU/L. The calcium-phosphorus product was 25.9. A homozygous nonsense variants of ENPP1 gene, c.783C>G (p.Tyr261X) in exon 7 was identified in the patient. Both parents were heterozygous carriers. Literature review identified 3 Chinese patients from one publication and 17 cases from twenty one publications around the world. None of the patients was found PHEX variants which is the most common variants among hypophosphatemic rickets patients. The disease onset age was 11 months to 10 years. Eight patients had short stature, five patients had the history of generalized arterial calcification of infancy. Four suffered from deafness, three showed localized calcifications of arteries, three patients manifested pseudoxanthoma elasticum and two suffered from ossification of posterior longitudinal ligament. Nine missense variants, six splicing variants and 4 nonsense variants were reported among these twenty patients. c.783C>G was found in two Chinese patients. Conclusion ENPP1 gene mutation was a cause of patient with hypophosphatemic rickets. Comorbid features included generalized arterial calcification of infancy, early onset hearing loss, pseudoxanthoma and ossification of posterior longitudinal ligament. ENPP1 gene testing should be performed on hypophosphatemic rickets patients without PHEX gene variants. Long-term follow up is recommended. The most common types of ENPP1 gene variants were nonsense/splicing variants. The gene c.783C>G was the most common variants in Chinese patients.

A 6-month-oldgirl was admitted in Affiliated Children′s Hospital of Capital Institute of Pediatrics with the complaint of “Recurrent fractures within 3 months”. She presented with frequent fractures, skeletal deformities,and distinctive facial features, including wide forehead, ocular proptosis and a flat nose bridge. She was diagnosed as osteoporosis imperfecta based on the clinical characteristics and given pamidronate disodium treatment. The whole exon sequencing showed heterozygous mutation of P4HB gene c.1178A>G (p.Y393C), which leads to a rare type of osteoporosis imperfect a Cole-Carpenter syndrome-1. Eight cases of osteoporosis imperfecta affected by P4HB mutation involving 5 mutationsites were retrieved from literature review. Different mutation sites lead to different clinical manifestations and severity of disease. The genotype-phenotype correlation of osteoporosis imperfect may be associated with the domains of coding proteins.

Objective:To explore the clinical and genetic basis for a patient with isolated 17, 20 lyase deficiency presenting with pubertal gynecomastia.Methods:Clinical manifestation, steroid analysis as well as genetic testing were carried out for a 14-year-old boy featuring puberty gynecomastia.Results:The patient was admitted due to puberty gynecomastia for 2 years. Physical examination showed Tanner B5, G2 and normal blood pressure. Laboratory examination showed normal range of serum potassium and blood gas. Steroid analysis revealed extremely high pregnenolone, progesterone, 17-hydropregnenolone and 17-hydroprogesterone, Correspondingly, the DHEA, androstenedione, testosterone and dihydrotestosterone were low. He was found to harbor compound heterozygous variants of CYP17A1 gene (c.1304T>C/p.F435S and c. 1346G>A/p.R449H), among which the R449H variant may result in isolated 17, 20 lyase deficiency by altering the structure of redox-partner binding site. Conclusion:Isolated 17, 20 lyase is a rare cause for puberty gynecomastia. The p. R449H variant of the CYP17A1 gene can result in isolated 17, 20 lyase deficiency.

Objective : To investigate the application of indocyanine green in near-infrared fluorescence imaging to determine the scope of necrotic bone resection in osteoradionecrosis of the jaw and to provide a reference for clinicians Methods : Eight patients with osteoradionecrosis of the jaws were enrolled. Indocyanine green was intravenously injected through the elbow vein 10 minutes before osteotomy. After conservative resection of necrotic bone lesions based on imaging results, the scope of potential dead bone resection in the area of low fluorescence intensity was gradually expanded at an initial distance of 0.3 cm. Near-infrared fluorescence imaging and fluorescence intensity determination of bone cross-section were performed before and after extended resection. Statistical differences were analyzed. All patients with osteonecrosis underwent regular follow-up to evaluate the postoperative efficacy Results: Indocyanine green was injected into all 8 patients with osteoradionecrosis for near-infrared fluorescence imaging and the scans were clear; the fluorescence intensity of fresh bone wounds with an expanded mandibular resection range of (0.95 ± 0.14) cm was (226.2 ± 15.8) au, which was higher than that based on intraoperative macroscopic observation and radiological results (108.8 ± 3.4) au, (t = 20.718, P<0.001). The postoperative follow-up improvement rate of 8 patients was 87.5%. Conclusion Near-infrared fluorescence imaging with indocyanine green can assist in the successful removal of necrotic bone until fresh bleeding of the jaw wound occurs, which has important clinical value in defining the resection range of osteoradionecrosis of the jaw.