Humans ; Osteogenesis Imperfecta/diagnosis*

OBJECTIVE: To identify the pathogenic variant for a husband with osteogenesis imperfecta and provide preimplantation genetic testing (PGT) for the couple. METHODS: High-throughput sequencing and Sanger sequencing were carried out to identify the pathologic variant in the husband patients. PGT of embryos was performed through direct detection of the mutation site. Meanwhile, chromosome aneuploidy of the blastocysts was screened. Following transplantation, cytogenetic and genetic testing of fetal amniotic fluid sample was carried out during mid-pregnancy. Chromosome copy number variant (CNV) was detected at multiple sites of the placenta after delivery. RESULTS: The husband was found to harbor heterozygous c.544-2A>G variant of the COL1A1 gene. The same variant was not detected in either of his parents. PGT revealed that out of three embryos of the couple, one was wild-type for the c.544-2A site but mosaicism for duplication of 16p13.3.11.2. The other two embryos were both heterozygous for the c.544-2A>G variant. Following adequate genetic counseling, the wild-type embryo was transplanted. Amniotic fluid testing confirmed that the fetus had normal chromosomes and did not carry the c.544-2A>G variant. The copy number of chromosomes at different parts of placenta was normal after birth. CONCLUSION For couples affected with monogenic disorders, e.g., osteogenesis imperfecta, direct detection of the mutation site may be used for PGT after identifying the pathogenic variant. After adequate genetic counseling, prenatal diagnosis must be carried out to ensure the result.
Aneuploidy ; China ; Female ; Genetic Testing ; Humans ; Osteogenesis Imperfecta/genetics* ; Pregnancy ; Preimplantation Diagnosis

OBJECTIVE: To carry out preimplantation genetic testing (PGT) for a couple where the husband was affected by osteogenesis imperfecta combined with balanced translocation using the karyomapping technique. METHODS: Blastocysts were detected using karyomapping, the carrier status of COL1A1 c.760G>A (p.Gly254Arg) variant and the carrier status of the translocated chromosome were analyzed simultaneously. RESULTS: For a total of 10 blastocysts, two euploid blastocysts were found to not carry the COL1A1 c.760G>A (p.Gly254Arg) variant but a balanced translocation. After transplanting one of the blastocysts, clinical pregnancy was achieved. Amniocentesis at 18th gestational week and prenatal genetic testing was in keeping with the result of PGT.A healthy female was born at 40+4 weeks gestation. CONCLUSION For patients simultaneously carrying genetic variant and balanced chromosomal translocation, PGT can be performed with efficiency by the use of karyomapping method.
Blastocyst ; Female ; Fertilization in Vitro ; Genetic Testing ; Humans ; Osteogenesis Imperfecta/genetics* ; Pregnancy ; Preimplantation Diagnosis ; Spouses ; Translocation, Genetic

OBJECTIVE: To explore the genetic basis for a couple with normal phenotype but repeated pregnancies with fetuses affected by osteogenesis imperfecta. METHODS: Whole exome sequencing (WES) was carried out on fetal specimens and parental DNA to detect potential pathologic variants. Suspected variants were verified by Sanger sequencing. Semen sample of the husband was collected for the extraction of genome DNA, and whole genome amplification (WGA) was performed for single sperms isolated from the sample. RESULTS: WES has identified a heterozygous c.1378G>A (p.G460S) variant of the COL1A2 gene in the fetus, which was predicted to be pathogenic but not detected in peripheral blood samples of both husband and wife. The heterozygotic variant was detected in semen DNA from the husband. Among 15 spermatozoa, 4 were found to harbor the variant. CONCLUSION The fetus was diagnosed with osteogenesis imperfecta, and the gonadal mosaicism probably accounted for the repeated abnormal pregnancies. Possibility of gonadal mosaicism should be considered when counseling couples with normal phenotype and genotype but recurrent abnormal pregnancies and/or births of children with similar phenotypes and genetic variants.
Adult ; Child ; Collagen Type I ; genetics ; Female ; Fetus ; Gonadal Disorders ; genetics ; Humans ; Male ; Mosaicism ; Mutation ; Osteogenesis Imperfecta ; diagnosis ; genetics ; Pregnancy ; Prenatal Diagnosis ; Whole Exome Sequencing

This is a retrospective review of two adult siblings with osteogenesis imperfecta (OI) type III (according to Sillence classification), who sustained a spontaneous femoral neck fracture and subsequent nonunion. The diagnosis of OI in these two patients was made based on clinical, radiological and genetic findings. The fracture was most likely caused by femoroacetabular impingement secondary to OI induced acetabular protrusio. A valgus osteotomy according to Pauwels'principles and fixation of the osteotomy and nonunion with a locking plate resulted in healing despite compromised bone quality and limited bone stock. Long-term follow up (4.5 years and 6.5 years, respectively) is provided. When treating this difficult problem, improving the mechanobiological environment and decreasing the femoroacetabular impingement by a Pauwels type osteotomy should be considered.
Acetabulum ; Adult ; Diagnosis ; Femoracetabular Impingement ; Femoral Neck Fractures ; Femur Neck ; Follow-Up Studies ; Humans ; Osteogenesis Imperfecta ; Osteogenesis ; Osteotomy ; Retrospective Studies ; Siblings

OBJECTIVETo detect potential mutations of COL1A1 and COL1A2 genes in four Chinese pedigrees affected with osteogenesis imperfecta (OI) and provide prenatal diagnosis for a fetus at 18th gestational week.

METHODSAll coding regions and exon/intron boundaries of the COL1A1 and COL1A2 genes were analyzed with targeted next-generation sequencing (NGS). Suspected mutations were confirmed with Sanger sequencing in the probands, unaffected relatives and 200 unrelated healthy individuals. Prenatal diagnosis for a high-risk fetus was carried out through Sanger sequencing.

RESULTSThe probands of families 1 and 2 have respectively carried a c.760G>A (p.Gly254Arg) and a c.608G>T (p.Gly203Val) mutation of the COL1A1 gene. For family 3, the proband and his daughter have carried a novel c.299-1G>C splicing mutation of the COL1A1 gene. The same mutation was not found in the fetus of this family. For family 4, the proband has carried a novel c.1990G>C (p.Gly664Arg) mutation of the COL1A2 gene. The four mutations were not found in the unaffected relatives and 200 unrelated healthy individuals.

CONCLUSIONThe mutations of the COL1A1 and COL1A2 genes probably underlie the disease in the four families. NGS combined with Sanger sequencing can provide an effective and accurate method for their genetic and prenatal diagnosis.

Adult ; Child, Preschool ; Collagen Type I ; genetics ; DNA Mutational Analysis ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Infant, Newborn ; Male ; Mutation ; Osteogenesis Imperfecta ; genetics ; Prenatal Diagnosis

One-year-old male Persian cat presented with multiple fractures and no known traumatic history. Marked decrease of bone radiopacity and thin cortices of all long bones were identified on radiography. Tentative diagnosis was osteogenesis imperfecta, a congenital disorder characterized by fragile bone. To determine bone mineral density (BMD), quantitative computed tomography (QCT) was performed. The QCT results revealed a mean trabecular BMD of vertebral bodies of 149.9 ± 86.5 mg/cm³. After bisphosphonate therapy, BMD of the same site increased significantly (218.5 ± 117.1 mg/cm³, p < 0.05). QCT was a useful diagnostic tool to diagnose osteopenia and quantify response to medical treatment.
Animals ; Bone Density ; Bone Diseases, Metabolic ; Cats* ; Congenital, Hereditary, and Neonatal Diseases and Abnormalities ; Diagnosis ; Fractures, Multiple ; Humans ; Male ; Osteogenesis Imperfecta ; Osteogenesis* ; Radiography

Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Osteogenesis Imperfecta ; diagnosis ; therapy

Osteogenesis imperfecta (Ol) type V is distinct Ol phenotype that has recently been described. Patients with this phenotype present characteristically with interosseous membrane calcification and hyperplastic callus formation. We present the clinical and radiographic characteristics of two Filipino families diagnosed to have Ol type V. Through this review of cases, we aim to educate healthcare providers by highlighting salient clinical and radiographic features to aid in the recognition of this specific Ol phenotype, difficulties in diagnosis, current practices in management and fracture prevention, and issues in genetic counseling.

Human ; Osteogenesis Imperfecta ; Patients ; Bony Callus ; Phenotype ; Diagnosis ; Genetic Counseling

OBJECTIVETo detect mutation of COL1A1 gene in a Chinese family affected with type I osteogenesis imperfecta (OI) and to provide prenatal diagnosis for a fetus at 17th gestational week.

METHODSPolymerase chain reaction, DNA sequencing and restriction endonuclease analysis were used to verify the detected mutation among other members of the family and 100 healthy controls.

RESULTSNo mutation has been detected in the COL1A2 gene in all of the subjects. A heterozygous mutation c.104-1G>C was identified in the COL1A1 gene among all patients from this family. The same mutation was not found in other members from the family and the 100 healthy controls. The mutation was not found in the fetus, and was verified to be a new mutation according to the type I collagen mutation database.

CONCLUSIONThe c.104-1G>C mutation of the COL1A1 gene probably underlies the type I osteogenesis imperfecta in this family. Under the premise of a clear genetic diagnosis, prenatal diagnosis may be provided to reduce the risk for the disease.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child, Preschool ; Collagen Type I ; genetics ; DNA Mutational Analysis ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Infant, Newborn ; Male ; Molecular Sequence Data ; Osteogenesis Imperfecta ; diagnosis ; genetics ; Pedigree ; Point Mutation ; Pregnancy ; Prenatal Diagnosis