ADAMTSL2
- Known as:
- ADAMTSL2
- Catalog number:
- Y214354
- Product Quantity:
- 200ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ADAMTSL2
Related genes to: ADAMTSL2
- Gene:
- ADAMTSL2 NIH gene
- Name:
- ADAMTS like 2
- Previous symbol:
- -
- Synonyms:
- KIAA0605
- Chromosome:
- 9q34.2
- Locus Type:
- gene with protein product
- Date approved:
- 2005-01-12
- Date modifiied:
- 2016-10-05
Related products to: ADAMTSL2
Related articles to: ADAMTSL2
- Geleophysic dysplasia type 1 is a rare skeletal dysplasia caused by biallelic pathogenic variants in ADAMTSL2. Affected children typically show a "happy-natured facial appearance," postnatal short stature with acromelic limb shortening, progressive joint contracture, and skin tightness. Most patients are diagnosed in childhood, and very little is known about the neonatal manifestation. We report a Japanese girl with Geleophysic dysplasia type 1, whose neonatal manifestations were enough to raise suspicion of the disorder on retrospective clinical and radiological review. At birth, she presented with joint contractures, short digits, mild pulmonary stenosis, and a normal facial appearance, and later developed severe short stature, camptodactyly, gait disturbance, and a round face with a flat nasal bridge and upslanting palpebral fissures. The clinical constellation led to a suspicion of Geleophysic dysplasia type 1 at age 3 years, and exome sequencing revealed variants in ADAMTSL2, a recurrent pathogenic missense variant (p.Ser635Leu) and a novel nonsense variant (p.Cys666*). On radiological grounds, she manifested with the same skeletal alterations in the neonatal period and at age 3 years, including severe brachydactyly with cone-shaped epiphyses and metaphyseal broadening. The distinctive skeletal phenotype overlapped with that of Al-Gazali skeletal dysplasia, an ADAMTSL2-associated potentially lethal skeletal dysplasia, suggesting a phenotypic continuum between both entities. The present case suggests that a subset of Geleophysic dysplasia type 1 may present with diagnostic physical and radiological manifestations in the neonatal period. Early recognition of neonatal skeletal features can facilitate prompt diagnosis and early clinical management for affected children. - Source: PubMed
Shimura KazuhiroTsujioka YukoKijima ToshihideIchihashi YosukeKushima ReikoNishimura GenHasegawa TomonobuNarumi Satoshi - The ADAMTS family are extracellular matrix (ECM) proteins and enzymes involved in regulating tissue structure and function. The ECM is a network of proteins and polysaccharides surrounding the cells that provide support and maintain cellular function. Mutations to proteins in the ECM lead to systemic connective tissue disorders by disrupting the structural integrity and maintenance of the ECM, resulting in ocular, musculoskeletal, skin, and cardiovascular abnormalities. Mutations that arise from the ADAMTS family lead to specific connective tissue disorders with distinct clinical characteristics. Here, we detail these distinct clinical features of major connective tissue disorders that arise from mutations in the ADAMTS family proteins. These include Ehlers Danlos syndrome arising from mutation in , Geleophysic Dysplasia from 2, Weill-Marchesani Syndrome from and , Ectopia lentis from , thoracic aortic aneurysms and dissection from , valvular disease in , and a further connective tissue disorder from mutations in This review details the mechanisms in which mutations to these genes impair the structure of the ECM, leading to the variety of phenotypic outcomes seen in connective tissue disorders. - Source: PubMed
Publication date: 2026/03/31
Alcocer Ana DRush Elizabeth HMead Timothy J - Emphysema is an important chronic obstructive pulmonary disease (COPD) phenotype characterized by the destruction of air spaces distal to the terminal bronchiole. Aiming to detect potential emphysema biomarkers and to assess the systemic effects of emphysema in blood plasma, we conducted a small cross-sectional shotgun proteomics study. This study included N = 40 participants divided into four subgroups (N = 10 per group): patients with emphysema and COPD (CE), patients with COPD but without emphysema (CN), healthy smokers (HS) and healthy never-smokers (HN). The participants were sampled non-probabilistically to be similar in terms of age, sex and comorbidities. Participants' blood plasma was analyzed using liquid chromatography-mass spectrometry. Bioinformatic analysis included detection of differentially expressed proteins (DEPs) and overrepresentation analysis (ORA). Across all groups, a total of 994 proteins were identified, with NADP-dependent malic enzyme (NADP-ME; encoded by ) being the only DEP in the CE vs. CN contrast. Proteins such as BMP1, ADAMTSL-2, -4 and IGFBP4, -5, 6 were identified to be upregulated in CE vs. HN. Fibulin-1, -3 and several immunoglobulin components were identified to be downregulated in the CE vs. HN contrast. ORA revealed several enriched processes, including serine-type endopeptidase activity, insulin-like growth factor I and II binding, and signaling receptor binding. We propose NADP-ME, an important enzyme of intermediary metabolism and redox homeostasis, as a potential biomarker candidate of emphysema. Notably, NADP-ME is also implicated in anoikis resistance. Additionally, changes in the expression levels of BMP1, ADAMTSL-2 and -4, and fibulin suggest potential major systemic effects of extracellular matrix perturbation. As all data was derived from LC-MS analysis, these findings need to be further evaluated with complementary methods. - Source: PubMed
Publication date: 2026/03/21
Salai GrgurNovak RuđerHrkač StelaPustka VáclavPotěšil DavidZdráhal ZbyněkLjubicic DivoGrgurević Lovorka - Geleophysic dysplasia (GD) is caused by recessive mutations in ADAMTSL2 (a disintegrin and metalloprotease with thrombospondin type I motifs-2; GD1), or dominant mutations in FBN1 (GD2) or LTBP3 (GD3). GD is characterized by severe short stature and other skeletal abnormalities, characteristic facial features, thick skin, and hypermuscular build. Life-threatening complications can arise from progressive heart valve disease and narrowing of the large airways, resulting in approximately 33% mortality before the age of 5 years. Despite high childhood mortality and significant morbidity, no disease-modifying treatments exist for GD. To model disease progression and enable efficacy testing of mechanism-based therapeutic approaches, a mouse model for severe GD1 was generated by introducing the patient-specific ADAMTSL2 c.499G>A (p.D167N) mutation into the mouse Adamtsl2 locus. Homozygous Adamtsl2 (D167N) mice had reduced postnatal survival and developed short stature. Radiographs demonstrated significantly shortened hind limb and forelimb bones with delayed mineralization and abnormally shaped vertebrae. Histologic investigation revealed a shortened growth plate, suggesting abnormalities in chondrogenesis. Cardiac histomorphometry revealed dysplastic aortic heart valves, consistent with progressive heart valve disease observed in patients with GD1. In the lungs, bronchial obstruction was observed, as previously reported for global Adamtsl2 knockout mice, likely resulting in occlusion of the affected airways. Thus, the ADAMTSL2 D167N mouse model recapitulates key clinical manifestations of patients with GD1. - Source: PubMed
Publication date: 2026/03/19
Lin ConnieSivakumar Divya IAlcocer Ana DGavalas Sophia TTaye NandarajSeifert Deborah EBalic ZerinaMead Timothy JHubmacher Dirk - Geleophysic dysplasia represents an exceedingly uncommon autosomal recessive skeletal disorder marked by profound growth restriction, contractures affecting multiple joints, and cardiac valve abnormalities. The molecular foundation involves gene mutations disrupting extracellular matrix architecture. We document a 29-year-old Taiwanese woman followed longitudinally for 25 years, presenting with severe short stature measuring 141.2 cm, widespread joint contractures, thoracolumbar scoliosis, and distinctive gait abnormalities. Whole-exome sequencing identified compound heterozygous mutations: c.286C>T resulting in p. Arg96Trp and c.454_459del causing p. Cys152_Thr153del deletion. The clinical course revealed musculoskeletal deterioration alongside mild mitral valve involvement and os odontoideum. Bilateral glaucoma, consistent with previously reported ocular manifestations in geleophysic dysplasia, was diagnosed at age 26. Notably, recent ophthalmologic evaluation revealed keratoconus-like corneal ectasia with paradoxically increased central corneal thickness measuring 690-693 μm bilaterally, substantially exceeding normal values of 520-560 μm. This paradoxical corneal thickening, contrasting with the stromal thinning characteristic of classical keratoconus, represents a novel -related corneal phenotype. The patient maintained normal intellectual capacity despite physical limitations, contrasting with published early mortality rates approaching 33%. This extended clinical documentation establishes keratoconus-like corneal ectasia with paradoxical corneal thickening as a novel ophthalmologic manifestation in geleophysic dysplasia, while adding to prior reports of glaucoma in this condition. These findings emphasize the necessity for comprehensive ophthalmologic monitoring in -related disorders and supporting multidisciplinary management strategies. - Source: PubMed
Publication date: 2026/01/26
Lee Chung-LinChuang Chih-KuangChiu Huei-ChingChang Ya-HuiTu Yuan-RongLo Yun-TingWu Jun-YiLin Hsiang-YuLin Shuan-Pei