Humans ; East Asian People ; Genetic Profile ; Mutation ; Osteochondrodysplasias/genetics*

Humans ; Female ; Tibet ; Kashin-Beck Disease/epidemiology* ; China ; Metabolomics

OBJECTIVE: To investigate the effectiveness of sequential plate internal fixation in the correction of Madelung deformity after ulnar osteotomy and shortening. METHODS: The clinical data of 13 patients with Madelung deformity admitted between September 2015 and July 2021 were retrospectively analyzed. There were 5 males and 8 females with an average age of 18.3 years ranging from 17 to 23 years. The disease duration ranged from 12 to 24 months, with an average of 17 months. Three cases had a clear history of trauma. All patients had external radial deviation deformity and limited movement of the ulnar deviation, and the ulnar impact pain was significant during ulnar deviation movement; 9 patients had limited wrist joint supination movement, and the supination movement was normal. In the first stage, ulnar osteotomy and shortening combined with external fixator were used to correct wrist deformity in 13 patients. After operation, bone transfer was performed 6 times per day, with adjustments made every 4 hours, which was 1 mm per day. After the osteotomy was in place, the ulnar plate internal fixation was performed to reconstruct the ulnar stability in the second stage. The Cooney wrist joint score was used to assess the pain, function, range of motion, flexion and extension range of motion, and grip strength of the wrist joint before operation and before the removal of internal fixator. The subjective feeling and appearance satisfaction of patients were recorded. RESULTS: After the second-stage operation, all the 13 patients were followed up 10-22 months, with an average of 15 months. The deformity of wrist joint disappeared after operation, and the flexion, extension, and ulnar deviation were basically normal. There was no complication such as ulnar impingement sign, nonunion or infection. Wrist function, pain, and range of motion were significantly improved after operation, except for 1 patient who had no significant improvement in rotation and pain. The ulnar internal fixator was removed at 10-18 months after the second-stage operation. The scores of pain, function, range of motion, flexion and extension range of motion, and grip strength in the Cooney wrist score before removal of internal fixator significantly improved when compared with those before operation ( P<0.05). Subjective and appearance satisfaction of patients were excellent in 9 cases, good in 3 cases, and fair in 1 case. CONCLUSION Ulnar osteotomy and shortening with sequential plate internal fixation for correction of Madelung deformity, with mild postoperative pain, can effectively avoid bone nonunion, improve wrist joint function, and have significant effectiveness.
Male ; Female ; Humans ; Adolescent ; Retrospective Studies ; Ulna/surgery* ; Osteochondrodysplasias ; Radius Fractures/surgery* ; Wrist Joint/surgery* ; Osteotomy ; Range of Motion, Articular ; Treatment Outcome

OBJECTIVE: To explore the clinical and genetic characteristics of a fetus with Melnick-Needles syndrome (MNS). METHODS: A fetus with MNS diagnosed at Ningbo Women and Children's Hospital in November 2020 was selected as the study subject. Clinical data was collected. Pathogenic variant was screened by using trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasonography of the fetus had shown multiple anomalies including intrauterine growth retardation, bilateral femur curvature, omphalocele, single umbilical artery, and oligohydramnios. Trio-WES revealed that the fetus has harbored hemizygous c.3562G>A (p.A1188T) missense variant of the FLNA gene. Sanger sequencing confirmed that the variant was maternally derived, whilst its father was of a wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+PM2_Supporting+PP3+PP4). CONCLUSION The hemizygous c.3562G>A (p.A1188T) variant of the FLNA gene probably underlay the structural abnormalities in this fetus. Genetic testing can facilitate accurate diagnosis of MNS and provide a basis for genetic counseling for this family.
Child ; Female ; Humans ; Pregnancy ; Abnormalities, Multiple/genetics* ; Fetal Growth Retardation ; Fetus ; Filamins/genetics* ; Genetic Counseling ; Mutation ; Osteochondrodysplasias

OBJECTIVE: To analyze the clinical features and genotype of a child with Schmid type metaphyseal chondrodysplasia. METHODS: Clinical data of the child and her parents was collected. The child was subjected to high-throughput sequencing, and candidate variant was verified by Sanger sequencing of her family members. RESULTS: Whole exome sequencing revealed that the child has harbored a heterozygous c.1772G>A (p.C591Y) variant of the COL10A1 gene, which was not found in either of her parents. The variant was not found in the HGMD and ClinVar databases, and was rated as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The heterozygous c.1772G>A (p.C591Y) variant of the COL10A1 gene probably underlay the Schmid type metaphyseal chondrodysplasia in this child. Genetic testing has facilitated the diagnosis and provided a basis for genetic counselling and prenatal diagnosis for this family. Above finding has also enriched the mutational spectrum of the COL10A1 gene.
Humans ; Child ; Female ; Mutation ; Osteochondrodysplasias/diagnosis* ; Heterozygote ; Molecular Biology

OBJECTIVE: To explore the clinical phenotypes and genetic diagnosis of 2 sporadic cases for cleidocranial dysplasia. METHODS: The clinical data of two cases of CCD admitted to the Third Affiliated Hospital of Zhengzhou University on December 16, 2021 and December 9, 2021 were analyzed retrospectively, and the whole exome sequencing (WES), chromosome microarray analysis and copy number variation sequencing were performed. RESULTS: The main ultrasonographic findings of the fetus had included poorly calcified skull bones, budging of parieto-occipital area, compression and deformation of skull, and loss of nasal bone. The infant's clinical phenotypes included delayed closure of anterior fontanelle, recurrent respiratory tract infection, growth retardation, and clavicular hypoplasia. By WES analysis, the fetus was found to harbor a heterozygous c.911_914delinsTTT variant of the RUNX2 gene, whilst the infant was found to harbor a heterozygous c.1008delT variant of the RUNX2 gene. Both variants were verified by Sanger sequencing to have occurred de novo. CONCLUSION For sporadic cases featuring cleidocranial dysplasia, prenatal ultrasonography is particularly important. Hypoplastic clavicle, skull calcification and nasal bone absence are the main features. Diagnosis should also be suspected for infants featuring growth retardation, recurrent respiratory tract infections and clavicular dysplasia. The identification of the c.911_914delinsTTT and c.1008delT variants of the RUNX2 gene has facilitated genetic counseling and prenatal diagnosis, and also expanded the mutational spectrum of the RUNX2 gene.
Female ; Humans ; Pregnancy ; Cleidocranial Dysplasia/genetics* ; Core Binding Factor Alpha 1 Subunit ; DNA Copy Number Variations ; Growth Disorders ; Retrospective Studies

Objective: To investigate the clinical presentation and genetic characteristics of malignant infantile osteopetrosis. Methods: This was a retrospective case study. Thirty-seven children with malignant infantile osteopetrosis admitted into Beijing Children's Hospital from January 2013 to September 2022 were enrolled in this study. According to the gene mutations, the patients were divided into the CLCN7 group and the TCIRG1 group. Clinical characteristics, laboratory tests, and prognosis were compared between two groups. Wilcoxon test or Fisher exact test were used in inter-group comparison. The survival rate was estimated with the Kaplan-Meier method and the Log-Rank test was used to compare the difference in survival between groups. Results: Among the 37 cases, there were 22 males and 15 females. The age of diagnosis was 0.5 (0.2, 1.0) year. There were 13 patients (35%) and 24 patients (65%) with mutations in CLCN7 and TCIRGI gene respectively. Patients in the CLCN7 group had an older age of diagnosis than those in the TCIRGI group (1.2 (0.4, 3.6) vs. 0.4 (0.2, 0.6) years, Z=-2.60, P=0.008). The levels of serum phosphorus (1.7 (1.3, 1.8) vs. 1.1 (0.8, 1.6) mmol/L, Z=-2.59, P=0.010), creatine kinase isoenzyme (CK-MB) (457 (143, 610) vs. 56 (37, 82) U/L, Z=-3.38, P=0.001) and the level of neutrophils (14.0 (9.9, 18.1) vs. 9.2 (6.7, 11.1) ×10⁹/L, Z=-2.07, P=0.039) at diagnosis were higher in the CLCN7 group than that in the TCIRG1 group. However, the level of D-dimer in the CLCN7 group was lower than that in the TCIRGI group (2.7 (1.0, 3.1) vs. 6.3 (2.5, 9.7) μg/L, Z=2.83, P=0.005). After hematopoietic stem cell transplantation, there was no significant difference in 5-year overall survival rate between the two groups (92.3%±7.4% vs. 83.3%±7.6%, χ²=0.56, P=0.456). Conclusions: TCIRGI gene mutations are more common in children with osteopetrosis. Children with TCIRGI gene mutations have younger age, lower levels of phosphorus, CK-MB, and neutrophils and higher level of D-dimer at the onset. After hematopoietic stem cell transplantation, patients with CLCN7 or TCIRGI gene mutations have similar prognosis.
Child ; Male ; Female ; Humans ; Osteopetrosis/therapy* ; Retrospective Studies ; Prognosis ; Genes, Recessive ; Phosphorus ; Chloride Channels/genetics* ; Vacuolar Proton-Translocating ATPases/genetics*

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with microphthalmia. METHODS: Clinical data of the proband was collected. Whole exome sequencing (WES) was carried out to screen potential pathogenic variants in the proband. Candidate variant was verified by Sanger sequencing of the proband and his family members. Pathogenicity of the variant was predicted by searching the PubMed database and bioinformatic analysis. Sanger sequencing of amniotic fluid sample was carried out for prenatal diagnosis. RESULTS: The proband and his father were found to harbor a heterozygous c.151C>G (p.R51G) variant of the MAB21L2 gene. The same variant was not found in his mother and grandparents. Based on the guidelines of American College of Medical Genetics, the c.151C>G (p.R51G) variant was predicted as likely pathogenic. CONCLUSION The c.151C>G (p.R51G) variant of the MAB21L2 gene probably underlay the microphthalmia in the proband. Above finding has facilitated prenatal diagnosis for this pedigree.
China ; Coloboma ; Eye Proteins ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; Microphthalmos/genetics* ; Mutation ; Osteochondrodysplasias ; Pedigree ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To report on the clinical characteristics of a family of short-rib polydactyly syndrome type III and its pathogenic variants. METHODS: Muscle samples from the the third fetus was collected after the induction of labor, and peripheral blood samples of its parents and grandparents were also collected. Whole exome sequencing (WES) was carried out for the pedigree. Candidate variants were verified by Sanger sequencing of the family. RESULTS: The proband was found to harbor a c.9819+1G>A variant and a c.4625C>A variant of the DYNC2H1 gene, which were respectively inherited from its mother and father. Sanger sequencing verified that the family has fit the autosomal recessive inheritance. CONCLUSION The c.9819+1G>A and c.4625C>A variants of the DYNC2H1 gene probably underlay the short-rib polydactyly syndrome type 3 in the proband.
Child ; Cytoplasmic Dyneins/genetics* ; Humans ; Mutation ; Pedigree ; Ribs ; Short Rib-Polydactyly Syndrome/genetics*

OBJECTIVE: To analyze the clinical features and pathogenic variant in a Chinese pedigree affected with cleidocranial dysplasia (CCD). METHODS: Clinical data of 8 patients from the pedigree was collected, including physical examination and X-ray images of head, face, spine, limbs, and mouth. Peripheral blood samples were collected from 6 affected members for the extraction of genomic DNA. The proband and other 3 patients were subjected to trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing of the other 2 affected members from the pedigree. RESULTS: This pedigree has included 22 members (8 affected) from four generations. Genetic testing revealed that the proband has harbored a novel pathogenic variant of the RUNX2 gene [NM_001024630: c.1268_1277del (p.P425Afs*56)], which was inherited from her mother and carried by all affected members in the pedigree. The same variant was not detected among the unaffected members, suggesting co-segregation with the phenotype. CONCLUSION The c.1268_1277del (p.P425Afs*56) variant of the RUNX2 gene probably underlay the pathogenesis of CCD in this pedigree. Genetic testing has facilitated the definite diagnosis and enabled prenatal diagnosis.
Humans ; Pregnancy ; Female ; Cleidocranial Dysplasia/genetics* ; Pedigree ; Core Binding Factor Alpha 1 Subunit/genetics* ; Phenotype ; China ; Mutation