Congenital Genetic Disorders Research Articles

Identification of a novel compound heterozygous SMG9 variants in a Chinese family with heart and brain malformation syndrome using whole exome sequencing

SMG9-deficiency syndrome, also known as heart and brain malformation syndrome, is a very rare congenital genetic disorder mainly characterized by brain, heart, and growth and developmental abnormalities. This syndrome is an autosomal recessive disease resulting from mutations in the SMG9 gene, which encodes a critical component of nonsense-mediated mRNA decay. Thus far, only twelve SMG9 deficiency patients have been reported with five novel homozygous SMG9 mutations. The most frequent characteristic features of these patients are facial dysmorphism, severe global developmental delay, intellectual disability, congenital heart disease, growth restriction, microcephaly, and brain abnormalities. Herein, whole exome sequencing was performed to identify novel compound heterozygous SMG9 variants (NM_019108.3: c.1318_1319delAG (p.Ser440*) and c.947A>G (p.His316Arg)) in the proband, who exhibited syndromic intellectual disability. Mutations were confirmed as segregating in his affected sister and other unaffected family members by Sanger sequencing. The patients we describe here have a similar dysmorphology profile associated with SMG9-deficiency syndrome. Comparing the phenotype with that of patients in published reports, our patients can walk independently and their growth parameters are normal. In addition, short stature, failure to thrive, and microcephaly were not observed. Possible residual function of the H316R SMG9 variant could explain the milder phenotype observed in our patients. Our report is the first description of a non-consanguineous Chinese pedigree with novel compound heterozygous variants in the SMG9 gene. The molecular confirmation of the patient expands the genetic spectrum of SMG9-deficiency syndrome, and the manifestation of SMG9-deficiency syndrome in the patient provides additional clinical information regarding this syndrome.

Teaching motor responses to a child with trisomy 18: A preliminary study

AbstractTrisomy 18 (T18) is a congenital genetic disease that causes multiple impairments, mainly in motor functioning. Few studies have investigated behavioral interventions with individuals with T18. In the current study, we tested an intervention to teach basic motor responses to a 30‐month‐old boy with T18. He had severe hypotonia and emitted only a few uncoordinated movements of his head and arms. We taught him a grasping response using a manual guidance procedure that included repeating the movement with full manual guidance 30 consecutive times and then recording independent responses. We then taught turning the page of a book, pressing a button on a toy, and hammering responses, sequentially, using an adapted version of the same procedure within a multiple‐probe design. The participant learned each target response at a progressively faster rate. We discuss the potential use of this procedure for children with T18 and other severe motor restrictions.

Whole exome sequencing revealed a large deletion in EDAof a Vietnamese patient with hypohidrotic ectodermal dysplasia

Hypohidrotic ectodermal dysplasia (HED) (OMIM # 305100) is a congenital genetic disorder caused by mutations in EDA (NM_001399) on chromosome X. Children with HED have the abnormal development of epidermal structures such as skin, hair, nails, teeth, and sweat glands. The present study aimed to detect mutations in EDA of a Vietnamese family with a son having only five teeth and no sweat glands, using whole exome sequencing (WES) and multiplex PCR. The results showed that patient had a deletion of exon 1 in EDA (c.2_396del), which is likely to be inherited from the healthy mother. The results will partly contribute to molecular studies on HED, helping in genetic counseling and disease treatment.

Alloplastic and Implant Materials for Bone Grafting: a Literature Review

Bone reconstruction aft er trauma, infection, tumour or congenital genetic disorder is an important subject of modern medicine usually relying on bone graft ing materials. Autologous bone or autograft is still considered the “gold standard” most eff ective in bone defect reconstruction and osseous regeneration. Having the advantages of autograft ing, a series of issues remain related to a limited donor material, painful graft taking and the risk of putative complications (nonunions, graft rejection, infection, iatrogenic fractures, post-microsurgery arteriovenous shunt thrombosis, etc.). Th erefore, improved biomaterials are demanded to adequately meet the autograft criteria. Choosing optimal graft materials becomes relevant, aside to the rationale of selecting new surgical techniques. Th e osteoconductive and osteoinductive property evaluation in modern osteoplastic materials comprises a research avenue into optimal graft development for osseous correction in maxillofacial surgery, neurosurgery, traumatology and orthopaedics. Such biomaterials can be combined with alloplastic graft s to attain the required properties of osteoconduction, osteoinduction and osteogenesis. Th is analytic literature review focuses on current state-of-the-art in alloplastic graft ing that, in our opinion, grounds the progress of auto- and allograft innovative development.

Abstract 11616: Seizures in Infants with Congenital Heart Disease

Background: Infants with congenital heart disease (CHD) may have an increased risk to develop seizures during hospitalization. Objectives: to examine the association of CHD with non-epileptic, non-traumatic seizures in hospitalized infants up to one year of age. Methods: We conducted a retrospective analysis of the U.S. National Inpatient Sample dataset (2015-2018). We used the international classification of disease-10 th version to identify infants with different types of CHD. We included infants up to one year of age. We excluded infants <35 week gestational age, infants with central nervous system or with major congenital anomalies, common trisomy or genetic disorders. We used chi square testing to examine the association of subtypes of CHD with seizures excluding post traumatic and epileptic seizures. We calculated mortality in infants with CHD who developed seizures versus those who did not have seizures. Results: There was 12,023,781 infants in the weighted sample who met our inclusion criteria. Of them, 48.7% were females, 46.7% were Caucasians, 195,685 (1.63%) were identified with a CHD and 20,565 (0.17%) suffered at least one episode of seizure during hospitalization. Seizures occurred in 4225 (2.2%) of infants with any type of CHD compared to 16,340 (0.14%) in infants with no CHD, odds ratios for seizures is 15.6 (CI: 15.2-16.5, p <0.001). The association of seizures with subtypes of CHD is shown in table-1. Among infants with CHD, 2205 infants expired during hospitalization. Mortality was higher in infants with CHD who suffered seizures (8.5%) vs. those who did not have seizures (1.0%), OR 9.6 (8.5-10.8, p <0.001). Conclusion: Infants with CHD have a higher chance to experience seizure episodes during their hospitalization and those who have seizures have higher chances of mortality during hospitalization. Further analysis is required to understand the pathological correlation between seizures and CHD and its impact on long term developmental outcomes.

Genetic factors and cancer: diagnosis, prognosis and future perspectives

Genetics is specifically responsible for several pathologies or, at the least, it is associated with a wide range of them, either as a primary causal agent (congenital genetic diseases) or secondary, being a factor within several possible for a given disease. One of the most critical genetic concepts is developed from the phenotype, equivalent to the genotype associated with the environment. In other words, for a condition to manifest itself, cancer, for example, we need a genetic alteration within the environment, which somehow influences carcinogenesis from stochastic or induced interactions. Cancer cases are approximately 80% and 90% associated with external causes, and environmental changes are mainly motivated by human actions, habits, and behavior, leading to an increased risk of different types of cancer. These changes lead to the formation of a cycle since man promotes environmental changes, leading to genetic modifications responsible for 10-20% of cancer formation. Although the percentage seems not to be significant, we have, in fact, several genetic mechanisms that will lead to the emergence of the most diverse types of cancer, including polymorphisms, mutations, oxidative stress, oncogenes, and genes that regulate the cell cycle, including apoptosis.

Establishment of Down\u2019s syndrome periodontal ligament cells by transfection with SV40T-Ag and hTERT

Down’s syndrome is one of the most common human congenital genetic diseases and affected patients have increased risk of periodontal disease. To examine involvement of the disease with periodontal disease development, we established immortalized periodontal ligament cells obtained from a Down’s syndrome patient by use of SV40T-Ag and hTERT gene transfection. Expressions of SV40T-Ag and hTERT were observed in periodontal ligament cell-derived immortalized cells established from healthy (STPDL) and Down’s syndrome patient (STPDLDS) samples. Primary cultured periodontal ligament cells obtained from a healthy subject (pPDL) had a limited number of population doublings (< 40), while STPDL and STPDLDS cells continued to grow with more than 80 population doublings. Primary cultured periodontal ligament cells obtained from the patient showed a chromosome pattern characteristic of Down’s syndrome with trisomy 21, whereas STPDLDS samples showed a large number of abnormal chromosomes in those results. Gene expression analysis revealed that expression of DSCR-1 in STPDLDS is greater than that in STPDL. These results suggest that the newly established STPDLDS cell line may be a useful tool for study of periodontal disease in Down’s syndrome patients.

Analysis of the screening results for congenital adrenal hyperplasia involving 7.85 million newborns in China: a systematic review and meta-analysis

Background Congenital adrenal hyperplasia (CAH) is a group of congenital genetic diseases caused by defective steroidogenesis. Our study aims to systematically analyze the screening results for CAH in Chinese newborns. Methods Studies were searched from PubMed, Web of Science, Cochrane library and some Chinese databases up to September, 2020. Meta-analysis was performed after quality assessment and data extraction. Results After a review of 2 694 articles, we included 41 studies enrolling 7 853 756 newborns. In our study, we found that the incidence of CAH in China was 0.43‱ [95% confidence intervals(CI), (0.39‱, 0.48‱)], or 1/23 024 [95%CI, (1/25 757,1/20 815)]. 27 studies were included for analysis of the screening positive rate, which gave a rate of 0.66% [95%CI, (0.54%, 0.78%)]. As for the recall rate of positive cases, 17 studies were included and showed that the recall rate reached 86.17% [95%CI, (82.70%, 89.64%)]. Among the CAH patients, the ratio of males to females was 1.92:1 (119:62), and the ratio of salt wasting (SW) to simple virilization (SV) type was 3.25:1 (104:32). The average 17-hydroxyprogesterone (17-OHP) value of CAH was 393.40 ± 291.85 nmol/L (Range 33-1 300 nmol/L); there was no significant difference between male and female patients (437.17 ± 297.27 nmol/L v.s. 322.25 ± 293.04 nmol/L, P=0.16), but a significant difference was found between SW and SV patients (483.29 ± 330.07 nmol/L v.s. 73.80 ± 7.83nmol/L, P=0.04). Conclusion We systematically analyzed the current situation of neonatal CAH screening in China, which will deepen our understanding for future CAH screening and early diagnosis.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR): A Novel Genomic Modifying Technique

In a way akin to how technological advancements involving molecular and biological science rapidly developed during the last decade, CRISPR, a newly found genomic modifying technique, quickly gained the attention of the scientific community. This paper aims to provide a fundamental understanding of CRISPR technology by reviewing articles from several journals, consisting of general information about CRISPR technology, process, advantages, limitations, and comparisons with other technologies. This recent technology drastically altered the boundaries of genetic engineering-most notably due to its outstanding flexibility of gRNA modification, as demonstrated by the work of the two Nobel Prize award-winning scientists Emmanuelle Charpentier and Jennifer A. Doudna. From the journals that had been reviewed, this paper presents that the CRISPR-Cas9 is one of the most efficient tools for genetic engineering in our modern world because of its incredible potential to perform genetic material modification in a wide range of patients with greater efficiency, versatility, and accuracy than before, all the while being more cost-effective. Additionally, since significant research and newfound knowledge related to genetic science was made possible from the discovery of this CRISPR technology, the possibility of CRISPR-Cas9 treatment in patients-particularly to combat congenital genetic diseases-would become a horizon that is within the reach of humanity’s hands. Keywords: genomic modifying technique, CRISPR technology, genetic engineering, congenital genetic disease, genetic material modification.

Congenital anomalies and genetic disorders in neonates and infants: a single-center observational cohort study

Neonates with genetic disorders or congenital anomalies (CA) contribute considerably to morbidity and mortality in neonatal intensive care units (NICUs). The objective of this study is to study the prevalence of genetic disorders in an academic level IV NICU. We retrospective collected and analyzed both clinical and genetic data of all 1444 infants admitted to the NICU of the Radboudumc (October 2013 to October 2015). Data were collected until infants reached at least 2 years of age. A total of 13% (194/1444) of the patients were genetically tested, and 32% (461/1444) had a CA. A total of 37% (72/194) had a laboratory-confirmed genetic diagnosis. In 53%, the diagnosis was made post-neonatally (median age = 209 days) using assays including exome sequencing. Exactly 63% (291/461) of the patients with CA, however, never received genetic testing, despite being clinically similar those who did.Conclusions: Genetic disorders were suspected in 13% of the cohort, but only confirmed in 5%. Most received their genetic diagnosis in the post-neonatal period. Extrapolation of the diagnostic yield suggests that up to 6% of our cohort may have remained genetically undiagnosed. Our data show the need to improve genetic care in the NICU for more inclusive, earlier, and faster genetic diagnosis to enable tailored management.What is Known:• Genetic disorders are suspected in many neonates but only genetically confirmed in a minority.• The presence of a genetic disorder can be easily missed and will often lead to a diagnostic odyssey requiring extensive evaluations, both clinically and genetically.What is New:• Different aspects of the clinical features and uptake of genetic test in a NICU cohort.• The need to improve genetic care in the NICU for more inclusive, earlier, and faster genetic diagnosis to enable tailored management.

Identification of a Novel Stop Loss Mutation in P2RX2 Gene in an Iranian Family with Autosomal Nonsyndromic Hearing Loss

Background:Hearing loss, a congenital genetic disorder in human, is difficult to diagnose. WES is a powerful approach for ethiological disgnosis of such disorders. Methods:One Iranian family with two patients were attented in the study. Sequencing of known NSHL genes was carried out to recognize the genetic causes of HL. Results:Molecular analyses identified a novel stop loss mutation, c.1048T>G (p.Term350Glu), whitin the P2RX2 gene, causing a termination-site modification.This event would lead to continued translation into the 3' UTR of the gene, which in turn may result in a longer protein product. The mutation was segregating with the disease phenotype and predicted to be pathogenic by bioinformatic tools. Conclusion:This study is the first Iranian case report of a diagnosis of ADNSHL caused by P2RX2 mutation. The recognition of other causative mutations in P2RX2 gene more supports the probable function of this gene in causing ADNSHL.

Comparative analysis of congenital malformations of the fetus detected in the periods from 2010 to 2012 and from 2017 to 2019 (based on the materials of the maternity department of Rostov-on-Don)

Objective: to conduct a comparative analysis of the structure, number, and antenatal diagnosis of fetal malformations in two clinical groups. Materials and methods: a retrospective comparative analysis of the variations, frequency, and detectability of malformations and developmental abnormalities in newborns born in two groups was conducted for the periods from 2010 to 2012 (the first group) and from 2017 to 2019 (the second group). The study of these materials was conducted on the basis of the maternity department of the city hospital of Rostov-on-Don. Statistical processing of the obtained results was carried out using the programs Statistica 10 and Microsoft Excel 2013. Results: in the second group, the number of children with genital abnormalities increased. The number of children with skin abnormalities increased as well as the number of children with gastrointestinal malformations. There is a decrease in the number of abnormalities in the development of the musculoskeletal system and the circulatory system. The rate of cleavage of the lip and hard palate decreased. However, malformations of the fetus were not detected in all cases, although their detectability increased from 4.41% in 2010 – 2012 to 22.62% in 2017 – 2019, i.e. by 5.13 times. Conclusion. The search for modern, reliable, and non-invasive methods for diagnosing fetal malformations in early pregnancy is an important stage in the study of this issue. It is also important to train high-class ultrasound specialists as well as search for new biochemical markers of congenital genetic disorders.

Waardenburg syndrome type II in a Chinese pedigree caused by frameshift mutation in the SOX10 gene.

Waardenburg syndrome (WS) is a congenital hereditary disease, attributed to the most common symptoms of sensorineural deafness and iris hypopigmentation. It is also known as the hearing-pigmentation deficient syndrome. Mutations on SOXl0 gene often lead to congenital deafness and has been shown to play an important role in the pathogenesis of WS. We investigated one family of five members, with four patients exhibiting the classic form of WS2, whose DNA samples were analyzed by the technique of Whole-exome sequencing (WES). From analysis of WES data, we found that both the mother and all three children in the family have a heterozygous mutation on the Sex Determining Region Y - Box 10 (SOX10) gene. The mutation was c.298_300delinsGG in exon 2 of SOX10 (NM_006941), which leads to a frameshift of nine nucleotides, hence the amino acids (p. S100Rfs*9) are altered and the protein translation may be terminated prematurely. Further flow cytometry confirmed significant down-regulation of SOX10 protein, which indicated the SOX10 gene mutation was responsible for the pathogenesis of WS2 patients. In addition, we speculated that some other mutated genes might be related to disease phenotype in this family, which might also participate in promoting the progression of WS2.

Pediatric Dentistry and Oral Health Features of Children with Certain Genetic Diseases

Pediatric dentistry provides primary and comprehensive preventive and therapeutic dental care for infants and children in adolescence, as well as provides special medical needs. This specialty includes many skills, disciplines, procedures, and techniques that share a common origin with other dental specialties, but they have been modified and reformed to meet the special requirements of infants, children, adolescents, and special medical needs. However, pediatric dentistry is mainly focused on healthy children, while quite often there are cases when such assistance is required for children with congenital genetic diseases. The prevalence of rare diseases is approximately 65 cases per 100,000 people. This estimate reflects the existence of 7,000 different types of rare diseases, most of which are genetic in nature. Rare diseases of genetic origin are often associated with other comorbidities, which are often characterized by debilitating and chronically degenerative conditions associated with phenotypes. Patients with rare diseases may sometimes exhibit challenging behaviors and often experience physical, mental, and sensory impairments that can affect functioning and participation in daily life. The purpose of the work is to consider the features of pediatric dentistry and the features of oral health of children with certain genetic diseases.

Analysis of the Screening Results for Congenital Adrenal Hyperplasia Involving 7.85 Million Newborns in China: A Systematic Review and Meta-Analysis.

BackgroundCongenital adrenal hyperplasia (CAH) is a group of congenital genetic diseases caused by defective steroidogenesis. Our study aims to systematically analyze the screening results for CAH in Chinese newborns.MethodsStudies were searched from PubMed, Web of Science, Cochrane library and some Chinese databases up to September, 2020. Meta-analysis was performed after quality assessment and data extraction.ResultsAfter a review of 2 694 articles, we included 41 studies enrolling 7 853 756 newborns. In our study, we found that the incidence of CAH in China was 0.43‱ [95% confidence intervals(CI), (0.39‱, 0.48‱)], or 1/23 024 [95%CI, (1/25 757,1/20 815)]. 27 studies were included for analysis of the screening positive rate, which gave a rate of 0.66% [95%CI, (0.54%, 0.78%)]. As for the recall rate of positive cases, 17 studies were included and showed that the recall rate reached 86.17% [95%CI, (82.70%, 89.64%)]. Among the CAH patients, the ratio of males to females was 1.92:1 (119:62), and the ratio of salt wasting (SW) to simple virilization (SV) type was 3.25:1 (104:32). The average 17-hydroxyprogesterone (17-OHP) value of CAH was 393.40 ± 291.85 nmol/L (Range 33-1 300 nmol/L); there was no significant difference between male and female patients (437.17 ± 297.27 nmol/L v.s. 322.25 ± 293.04 nmol/L, P=0.16), but a significant difference was found between SW and SV patients (483.29 ± 330.07 nmol/L v.s. 73.80 ± 7.83nmol/L, P=0.04).ConclusionWe systematically analyzed the current situation of neonatal CAH screening in China, which will deepen our understanding for future CAH screening and early diagnosis.

Next-Generation Sequencing Technologies and Neurogenetic Diseases.

Next-generation sequencing (NGS) technology has led to great advances in understanding the causes of Mendelian and complex neurological diseases. Owing to the complexity of genetic diseases, the genetic factors contributing to many rare and common neurological diseases remain poorly understood. Selecting the correct genetic test based on cost-effectiveness, coverage area, and sequencing range can improve diagnosis, treatments, and prevention. Whole-exome sequencing and whole-genome sequencing are suitable methods for finding new mutations, and gene panels are suitable for exploring the roles of specific genes in neurogenetic diseases. Here, we provide an overview of the classifications, applications, advantages, and limitations of NGS in research on neurological diseases. We further provide examples of NGS-based explorations and insights of the genetic causes of neurogenetic diseases, including Charcot–Marie–Tooth disease, spinocerebellar ataxias, epilepsy, and multiple sclerosis. In addition, we focus on issues related to NGS-based analyses, including interpretations of variants of uncertain significance, de novo mutations, congenital genetic diseases with complex phenotypes, and single-molecule real-time approaches.

Difficult Airway Management in a Patient With Nicolaides-Baraitser Syndrome Who Had a Small Jaw and Limited Mouth Opening

Nicolaides-Baraitser syndrome (NCBRS) is a rare congenital genetic disorder characterized by distinctive facial features similar to Treacher Collins syndrome (TCS). We report the first case of successful nasal fiberoptic intubation in a patient with NCBRS with micrognathia and limited mouth opening due to trismus. A 9-year-old girl with NCBRS and dental caries was scheduled to undergo general anesthesia for a dental extraction. Initial attempts at oral intubation using a video laryngoscope were unsuccessful. However, subsequent attempts at nasal intubation using a flexible fiberoptic scope were successful. This report highlights that patients with NCBRS may present with difficult airways to manage and intubate.

Cardiovascular magnetic resonance (CMR) normal values for pulmonary arteries in healthy children and adolescents

Abstract Funding Acknowledgements Type of funding sources: None. Background Changes in the right ventricular outflow tract (RVOT) and pulmonary arteries (PAs) are often seen in paediatric patients with congenital heart disease (CHD), pulmonary hypertension or genetic disorders (e.g. Marfan syndrome, Loeys-Dietz syndrome, Williams syndrome, DiGeorge syndrome). Cardiovascular magnetic resonance (CMR) imaging is an excellent method to visualize the RVOT and PAs without the use of ionizing radiation and contrast media but for the interpretation of CMR data in the paediatric population the knowledge of normal values is crucial. However, normal values for pulmonary arteries from contrast-free cine CMR images are lacking. Purpose The aim of this retrospective multicentre study was to establish reference ranges for the diameters of the mean PA (MPA), right PA (RPA) and left PA (LPA). Methods 163 CMR scans of healthy children and adolescents (mean age 13.8 ± 2.9 years; range 5-18 years) from two centres in the UK and Germany were included. The diameter of the MPA was measured in sagittal-oblique RVOT cine images and transaxial cine stacks, whereas the diameter of the RPA and LPA were measured from transaxial stacks and specific pulmonary artery branch cine images. Results Mean systolic and diastolic diameters for the MPA were 22.1 ± 2.8 mm (14.4 ± 2.2 mm/m²)/ 17.2 ± 2.3 mm (11.3 ± 1.9 mm/m²) measured in RVOT cine stacks. Mean systolic and diastolic diameters for the RPA and LPA were: 1) RPA, 12.4 ± 1.7 mm (7,9 ± 1,6 mm/m²)/ 9.8 ± 1.6 mm (5.9 ± 1.8 mm/m²) and 2) LPA, 13.3 ± 1.5 mm (8.3 ± 2.1 mm/m²)/ 10.8 ± 1.5 mm (6.8 ± 1.8 mm/m²). Separate centile charts for boys and girls for the MPA were created. Conclusions We established CMR normal values for the MPA, RPA and LPA for children and adolescents. Our data might be useful for the detection of PA stenosis and dilatation and may serve as a reference in future studies.

Novel truncating mutations in ASXL1 identified in two boys with Bohring-Opitz syndrome

Bohring-Opitz syndrome (BOS, or BOPS) is a rare congenital genetic disorder with multisystem abnormalities characterized by significant craniofacial dysmorphism, feeding difficulties, severe developmental delay, profound intellectual disability, flexion of elbows with ulnar deviation, and flexion of the wrists and metacarpophalangeal joints. Here, we report two Chinese BOS patients with distinctive phenotypes caused by novel truncating mutations. One was a boy aged 5 years 9 months who had a novel c.1049G>A/p.Trp350* mutation in ASXL1 and displayed relatively mild BOS symptoms with autism features. The other was a 16-month-old boy who carried a novel c.2689delC/p.His897Ilefs*11 mutation and displayed typical BOS symptoms. New cases with novel mutations, along with a detailed clinical and molecular analysis are important for a better diagnosis and understanding of BOS.

Modification of COL1A1 in Autologous Adipose Tissue-Derived Progenitor Cells Rescues the Bone Phenotype in a Mouse Model of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a congenital genetic disorder mainly manifested as bone fragility and recurrent fracture. Mutation of COL1A1/COL1A2 genes encoding the type I collagen are most responsible for the clinical patients. Allogenic mesenchymal stem cells (MSCs) provide the potential to treat OI through differentiation into osteoblasts. Autologous defective MSCs have not been utilized in OI treatment mainly because of their impaired osteogenesis, but the latent mechanism has not been well understood. Here, the relative signaling abnormality of adipose-derived mesenchymal stem cells (ADSCs) isolated from OI type I mice (Col1a1+/-365 mice) was explored. Autologous ADSCs transfected by retrovirus carrying human COL1A1 gene was first utilized in OI therapy. The results showed that decreased activity of Yes-associated protein (YAP) due to hyperactive upstream Hippo kinases greatly contributed to the weakened bone-forming capacity of defective ADSCs. Recovered collagen synthesis of autologous ADSCs by COL1A1 gene modification normalized Hippo/YAP signaling and effectively rescued YAP-mediated osteogenesis. And the COL1A1 gene engineered autologous ADSCs efficaciously improved the microstructure, enhanced the mechanical properties and promoted bone formation of Col1a1+/-365 mice after femoral bone marrow cavity delivery and might serve as an alternative source of stem cells in OI treatment. © 2021 American Society for Bone and Mineral Research (ASBMR).