Objective A 10-years-old girl with Schimke immuno-osseous dysplasia ( SIOD ) was reported and a literature review presented to provide clinical and genetic information of this rare disease. Methods Retrospective analysis of a case of SIOD in Capital Institute of Pediatrics was reported. The patient and her parents' DNA were extracted from blood for detecting SMARCALl gene mutation. Literatures of the disease were reviewed. Results The patient was a ten-years-old girl who admitted because of slow growth in height for 3 years. Herstaturewas123cm(T(p.Q149X)andc.1933C>T(p.R645C)compound heterozygous mutation. A novel nonsense c.445C>T(p. Q149X)was found. One reported missense mutations c. 1933C>T(p. R645C) was detected. We reviewed literatures and found that there were 4 confirmed cases in China including this one. All the 4 cases had the characteristic of short stature, special facial features, osseous dysplasia, pigmentations in body, and proteinuria. However the severity of the disease and genetic changes are not the same. Conclusion When a patient was admitted because of short stature, diagnosis of SIOD should be suspected if he or she also had special facial feature, osseous dysplasia, café-au-lait spots, and proteinuria. Gene test is a tool to help us to make a definite diagnosis of SIOD.

Objective Congenital nephrogenic diabetes insipidus (CNDI) is a rare disease, the aim of this article is to help better understanding of this disease. Methods The clinical features, genetic analysis and treatments of two siblings with CNDI were retrospectively analyzed, and related literatures were reviewed. Results Both brothers had polydispia, polyuria and low concentrate urine continuously, and they both had a mutation in AQP 2 conifrmmed with Sanger sequencing. This novel frame shift mutation caused arginine of 254 to histidine, and prolonged AQP 2 protein. Conclusions Gene analysis can help diagnosis of CNDI. Amiloride is useful option for treatment.

Objective To analyze the genetic changes and detailed clinical presentations of 5 maturity-onset diabetes of the young (MODY) cases in order to enhance the knowledge about MODY in children.Methods Seventy-eight patients initially diagnosed as diabetes mellitus between January 1 and December 31,2015 in Capital Institute of Pediatrics were retrospectively studied.Nine of them were suspected of MODY,and 5 patients were diagnosed as MODY through gene test.Clinical informations were collected including age,gender,main complaint,family history,body mass index (BMI),fasting blood glucose,fasting blood insulin,2-hour blood glucose and insulin after oral glucose tolerance test and glycosylated hemoglobin.The blood glucose was monitored dynamically in 2 patients.Targeted capture panel was designed to capture the 16 genes related to MODY,including 12 genes from MODY1 to MODY13 type and 4 genes with weak evidence of MODY according to Human Gene Mutation Database Exome capture,and Next-Generation sequencing on a HiSeq2000 (Illumina) was performed.After bioinformatics analysis,all prioritized variants detected in patients were validated by Sanger sequencing,including the probands and their parents.Results Five patients were confirmed as MODY by molecular diagnosis,accounting for 6.4％ of all the 78 patients in 2015.The ratio of male to female was 2 ∶ 3.The ages at diagnosis ranged from 2 to 11 years old,and the median age was 3 years old.Two cases were found to have abnormal blood glucose in physical examination.The rest 3 cases were discovered with abnormal blood glucose during hospitalization because of pneumonia (1 case)or diarrhea (2 cases).In 4 cases,their mothers had gestational diabetes history,in 1 case the father suffering from diabetes.BMI ranged 15.68-23.40 kg/m2.Fasting blood glucose was 6.3-7.2 mmol/L.Fasting blood insulin was 0.5-8.0 IU/L.Glucose tolerance test results showed that blood glucose of the patients was 8.6-10.8 mmol/L after 2 hours.The level of glycosylated hemoglobin was 5.5％-6.7％.Blood glucose was 3.9-13.0 mmol/L.All the 5 confirmed patients were caused by GCK gene mutation (MODY2 type).The mutations detected were located at Exon7 (2 cases),Exon4 (1 case),Exon5 (1 case),and Exon10 (1 case).Conclusions All the confirmed MODY patients were identified either through medical exam or infectious disease,and all had positive family history.Their BMI ranged widely.Fasting blood glucose was slightly elevated and glycosylated hemoglobin was normal or slightly elevated,but fasting blood insulin was normal in all the patients.Abnormal glucose tolerance test results were found in all 5 patients.Glycosylated hemoglobin was normal or slightly elevated.MODY2 was the only subtype detected in this group,which indicated that the common type in children was different from that in adults.

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.

Objective To report clinical characteristics and genetic results of two sisters suffered from congenital adrenal cortex hyperplasia (17-α-hydroxylase deficiency), and relevant literatures were reviewed. Methods Clinical manifestation and laboratory examination data of two sister cases of 17-α-hydroxylase deficiency enrolled in Capital Institute of Pediatrics in March 2016 were analyzed. Sanger sequencing and MLPA for CYP17A1 genes were performed and the parents' genes were also verified. Results The two patients were four years and 10 years old, both suffered from hypokalemia after infections, and hypergonadotrophin gonad hypofunction. One case was with slightly high blood pressure. Laboratory test results showed potassium fluctuation tendency in 1.9~4.0 mmol/L, 17-OHP and DHEA was decreased. Enhanced CT showed different degree of adrenal gland enlargement. Chromosome examination of the older sister is 46, XY. Both sisters demonstrated heterozygous mutation of CYP17A1 gene. The molecular genetic analysis suggested a c.985_987delTACinsAA from father and a deletion spanning exons 1-7 of the CYP17A1 gene from mother. Conclusion 17-α-hydroxylase enzyme deficiency can be diagnosed before adolescence. Clinical hypokalemia with unknown reason and high blood pressure may indicate the disease. The diagnosis can be confirmed with gene sequencing of CYP17A1.

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.

OBJECTIVE: To explore the genetic basis for a child with neonatal severe hyperparathyroidism. METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Whole exome sequencing was carried out to screen potential mutations. Suspected mutation was verified by Sanger sequencing. RESULTS: The proband was found to carry compound heterozygous variants c.179G>A (p.Cys60Tyr) and c.1525G>A (p.Gly509Arg) of the CaSR gene. The c.179G>A variant was derived from her mother and was unreported previously. The c.1525G>A variant was derived from her father and known to be pathogenic. CONCLUSION The compound heterozygous variants of c.179G>A and c.1525G>A of the CaSR gene probably underlie the disease in the patient. The results of genetic testing has enabled diagnosis and genetic counseling for her family.
Female ; Genetic Counseling ; Genetic Testing ; Humans ; Hyperparathyroidism/genetics* ; Infant, Newborn ; Infant, Newborn, Diseases/genetics* ; Mutation ; Pedigree ; Receptors, Calcium-Sensing/genetics* ; Whole Exome Sequencing

OBJECTIVE: To summarize clinical manifestations and results of genetic testing in 12 children with Gitelman syndrome (GS). METHODS: Clinical data of the children was collected. Whole exome sequencing(WES) was carried out to screen potential variants of genomic DNA. Candidate variants were verified by Sanger sequencing. RESULTS: The patients have included 10 boys and 2 girls, whom were diagnosed at between 2.8 to 15.0 year old. Six patients were due to infections, 5 were due to short stature, and 1 was due to lower limb weakness. All patients were found to carry variants of SLC12A3 gene, which included 11 with compound heterozygous variants and 1 with homozygous variant. All of the 19 alleles of the SLC12A3 gene carried by the patients were delineated, which included 15 missense variants, 2 frameshift variants and 2 splice region variants. These variants were unreported previously, which included c.578_582dupCCACC (p.Asn195Profs*109), c.251C>T (p.Pro84Leu) and c.2843G>A (p.Trp948X). CONCLUSION The clinical symptoms of GS in children are atypical and often seen in older children. For children with occasional hypokalemia associated with growth failure, GS should be suspected. The majority of GS children carry two pathogenic variants of the SLC12A3 gene, mainly compound heterozygotes, among which p.Thr60Met is the most common one. The discovery of new variants has enriched the spectrum of SLC12A3 gene variants.
Adolescent ; Child ; Child, Preschool ; DNA ; Female ; Genetic Testing ; Gitelman Syndrome/genetics* ; Humans ; Hypokalemia/genetics* ; Male ; Solute Carrier Family 12, Member 3/genetics*

OBJECTIVE: To explore the clinical characteristics and genetic basis for three children with Congenital chlorine diarrhea (CCD). METHODS: Three children with CCD who attended the Affiliated Children's Hospital of Capital Pediatric Institute from June 2014 to August 2020 were selected as the research subjects. Peripheral blood samples of the three children and their parents were collected for genetic testing. And the results were verified by Sanger sequencing. RESULTS: The clinical manifestations of the three children have included recurrent diarrhea, with various degrees of hypochloremia, hypokalemia and refractory metabolic alkalosis. Genetic testing revealed that the three children have all carried variants of the SLC26A3 gene, including homozygous c.1631T>A (p.I544N) variants, c.2063_1G>T and c.1039G>A (p.A347T) compound heterozygous variants, and c.270_271insAA(p.G91kfs*3) and c.2063_1G>T compound heterozygous variants. Sanger sequencing confirmed that all of the variants were inherited from their parents. CONCLUSION The variants of the SLC26A3 gene probably underlay the CCD in these children. Above finding has enriched the spectrum of SLC26A3 gene variants.
Humans ; Child ; Chlorine ; Genetic Testing ; Hypokalemia/genetics* ; Homozygote ; Diarrhea/genetics* ; Mutation

The clinical data of a child with Van Wyk-Grumbach syndrome (VWGS) who visited Capital Institute of Pediatrics in 2019 were retrospectively analyzed. The patient was a seven year old girl, her main clinical manifestations included short stature (well below -2 standard deviations), obesity and breast development. The results of laboratory testing indicated that the level of thyrotropin (TSH)>100 mIU/L and the level of free thyroxine (FT 4) was 5.15 pmmol/L; serum estradiol and prolactin levels were significantly elevated; the gonadotropin-releasing hormone(GnRH) stimulation test showed that the gonad axis was not activated. She had giant ovarian cyst, pituitary hyperplasia, anemia and pericardial effusion. Bone age was delayed; and her blood lipids had increased. Therefore, she was diagnosed as Van Wyk-Grumbach syndrome. The patient received the treatment of levothyroxine, the drug does was gradually increased from 25 μg per day to 75 μg per day, vaginal bleeding was followed by medication for 3 days. Three months later, her thyroid function was back to normal, and giant ovarian cyst regressed, but the ovaries were bulky,pericardial effusion was absorbed. The levothyroxine dose was adjusted to 50 μg per day according to the test result of thyroid function. And 1 year late the thyroid function was normal, pituitary magnetic resonance imaging(MRI) showed the hyperplastic adenohypophysis was back to normal, no more vaginal bleeding occurred, and the giant ovarian cyst was shrunk.