Review
Genetics & Heredity
Alice Costantini, Alessandra Guasto, Valerie Cormier-Daire
Summary: This article discusses the importance of the TGF-beta and BMP signaling pathways in bone development and skeletal health, as well as the genetic variants associated with skeletal dysplasia. The review provides a detailed description of the clinical features of patients, genetic findings, and the molecular mechanisms underlying the disease. The advances in pharmacological treatment targeting TGF-beta are also discussed.
ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS
(2023)
Review
Pediatrics
Zi Qiang Glen Liau, Yuhang Wang, Hong-Yi Lin, Chin Kai Cheong, Shobhit Gupta, James Hoi Po Hui
Summary: This review discusses the management of pediatric short stature, particularly in the case of disproportionate short stature caused by skeletal dysplasia. Early recognition of short stature and appropriate referrals can help alleviate parental concern and provide comprehensive care for improved quality of life. Advancements in clinical diagnostic tools and treatment options provide optimism for managing pediatric short stature.
CURRENT OPINION IN PEDIATRICS
(2022)
Article
Orthopedics
Noor ul Ain, Zunaira Fatima, Sadaf Naz, Outi Makitie
Summary: This study identified genetic variants in two unrelated consanguineous families with skeletal dysplasia and short stature, showcasing different phenotypic characteristics. The findings expand the genotypic spectrum of RAB33B variants and highlight the phenotypic homogeneity of patients with PCNT variants.
BMC MUSCULOSKELETAL DISORDERS
(2021)
Review
Biochemistry & Molecular Biology
Wiktoria Wrobel, Emilia Pach, Iwona Ben-Skowronek
Summary: Achondroplasia is a genetic disorder caused by a mutation in the FGFR3 gene, leading to short stature. Treatment is necessary to improve quality of life and reduce complications, with recombinant human growth hormone being the current best option. Other drugs are still in early stages of clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Odette Ludwig-Peisker, Emily Ansel, Daniela Schweizer, Vidhya Jagannathan, Robert Loechel, Tosso Leeb
Summary: This study investigated disproportionate dwarfism in Vizsla dogs and proposed a new classification called skeletal dysplasia 3 (SD3). Through genome sequencing and genotype analysis, the study identified a mutation in the PCYT1A gene as a potential causative variant for this condition. The results of this study contribute to genetic testing and prevention of breeding affected Vizsla puppies.
Article
Genetics & Heredity
Sandra Hoffmann, Ralph Roeth, Sabrina Diebold, Jasmin Gogel, David Hassel, Steffen Just, Gudrun A. Rappold
Summary: SHOX deficiency leads to a range of clinical phenotypes, including skeletal dysplasia and short stature. By analyzing differentially expressed genes, novel SHOX target genes were identified. Validation in zebrafish models showed dysregulation of multiple genes in shox-deficient pectoral fins, indicating their importance in SHOX-related growth disorders.
FRONTIERS IN GENETICS
(2021)
Article
Cell Biology
Baoheng Gui, Chenxi Yu, Xiaoxin Li, Sen Zhao, Hengqiang Zhao, Zihui Yan, Xi Cheng, Jiachen Lin, Haiyang Zheng, Jiashen Shao, Zhengye Zhao, Lina Zhao, Yuchen Niu, Zhi Zhao, Huizi Wang, Bobo Xie, Xianda Wei, Chunrong Gui, Chuan Li, Shaoke Chen, Yi Wang, Yanning Song, Chunxiu Gong, Terry Jianguo Zhang, Xin Fan, Zhihong Wu, Yujun Chen, Nan Wu
Summary: This study investigated the mutational spectrum of ROR2 in children with short stature and identified several mutations that potentially disrupt the expression of downstream genes in the Wnt5a-ROR2 pathway by affecting protein subcellular localization and expression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pediatrics
Janet M. Legare, Donald Basel
Summary: Children with short stature due to skeletal dysplasia are often referred to pediatric endocrinologists. This primer presents information on when to be concerned about skeletal dysplasia, how to evaluate it, and recent and upcoming therapies.
FRONTIERS IN PEDIATRICS
(2023)
Article
Pediatrics
M. Willems, C. Amouroux, M. Barat-Houari, J. -P. Salles, T. Edouard
Summary: This article discusses the importance of treatment and genetic diagnosis in statural growth, explaining the regulatory factors and pathological conditions associated with growth retardation and genetic variants.
ARCHIVES DE PEDIATRIE
(2022)
Article
Medicine, General & Internal
Maria-Christina Ungureanu, Anamaria Hrisca, Lavinia Caba, Laura Teodoriu, Stefana Bilha, Cristina Preda, Letitia Leustean
Summary: Children with idiopathic short stature (ISS) are often underdiagnosed and may have genetic causes related to growth plate regulation or GH-IGF1 axis physiology. This study presents a family of five children initially diagnosed with ISS or familial short stature, but later found to have SHOX gene deficiency. Clinical signs and radiological characteristics can indicate the presence of SHOX deficiency. Treatment with rGH is approved for children with SHOX gene deficiency, but individualized investigation is necessary for optimal management.
Article
Endocrinology & Metabolism
Meiping Chen, Hui Miao, Hanting Liang, Xiaoan Ke, Hongbo Yang, Fengying Gong, Linjie Wang, Lian Duan, Shi Chen, Hui Pan, Huijuan Zhu
Summary: Clinical genetic evaluation is an important tool for understanding the causes of growth disorders. This study explores the genetic architecture of short-stature children with skeletal abnormalities and evaluates the frequency of collagenopathies, including the response to recombinant human growth hormone (rhGH) treatment.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Medicine, General & Internal
Li Zhang, Jinling Wang, Guanping Dong, Dingwen Wu, Wei Wu
Summary: X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) is a rare hereditary cause of short stature in childhood. This case report identified a novel missense variant in the TRAPPC2 gene, and the patient showed height gain with growth hormone treatment but had to stop due to elevated glucose levels.
Review
Genetics & Heredity
Huixiao Wu, Shuping Wang, Guimei Li, Yangyang Yao, Ning Wang, Xiaoqing Sun, Li Fang, Xiuyun Jiang, Jiajun Zhao, Yanzhou Wang, Chao Xu
Summary: A novel heterozygous variant in the COL10A1 gene was identified in a 2-year-old Chinese boy with pathogenic predicted effects on protein structure. Genotype-phenotype correlation analysis indicated that variants in the NC1 domain were associated with earlier onset and more severe symptoms in SMCD patients.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Wenqi Chen, Yazhou Li, Jing Zhang, Yufan Yuan, Donglan Sun, Jiayu Yuan, Kai Yang, Ying Liang, Qing Guo
Summary: This study identified two compound heterozygous variations in the DYNC2H1 gene, including a novel deletion of exon (64-83), through whole-exome sequencing. These findings clarified the cause of fetal skeletal dysplasia in two families, provided guidance for their future pregnancies, and emphasized the value of WES in diagnosing skeletal dysplasia with unclear prenatal indications.
FRONTIERS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Aditya Saxena, Virag Sharma, Pushpanathan Muthuirulan, Stanley J. Neufeld, Mai P. Tran, Haydee L. Gutierrez, Kevin D. Chen, Joel M. Erberich, Amanda Birmingham, Terence D. Capellini, John Cobb, Michael Hiller, Kimberly L. Cooper
Summary: This study compares the genetic mechanisms of mouse and jerboa skeletal elongation and identifies genes and pathways associated with the disproportionately rapid elongation of jerboa feet. The study also identifies transcription regulators that might play a key role in genome expression differences between species, with Shox2 being expressed in jerboa metatarsals where it is not detected in other vertebrates. The findings provide a framework for understanding the genetic control of skeletal growth and the malleability of vertebrate limb proportion.