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Acanthamoeba castellanii is a widespread Free-Living Amoeba (FLA) that can cause severe ocular or cerebral infections in immunocompetent and immunocompromised patients, respectively, besides its capacity to transport diverse pathogens. During their life cycle, FLA can alternate between a vegetative form, called a trophozoite, and a latent and resistant form, called a cyst. This resistant form is characterized by the presence of a cell wall containing two layers, namely the ectocyst and the endocyst, mainly composed of cellulose and proteins. In the present work, we aimed to stimulate Acanthamoeba castellanii excystment by treating their cysts with a cellulolytic enzyme, i.e., cellulase, or two proteolytic enzymes, i.e., collagenase and pepsin. While 11 days were necessary to obtain total excystment in the control at 27°C, only 48 h were sufficient at the same temperature to obtain 100% trophozoites in the presence of 25 U/mL cellulase, 50 U/mL collagenase or 100 U/mL pepsin. Additionally, more than 96% amoebae have excysted after only 24 h with 7.5 U/mL cellulase at 30°C. Nevertheless, no effect of the three enzymes was observed on the excystment of Balamuthia mandrillaris and Vermamoeba vermiformis. Surprisingly, A. castellanii trophozoites excysted in the presence of cellulase displayed a markedly shorter doubling time at 7 h, in comparison to the control at 23 h. Likewise, trophozoites doubled their population in 9 h when both cellulose and cellulase were added to the medium, indicating that Acanthamoeba cyst wall degradation products promote their trophozoite proliferation. The analysis of cysts in epifluorescent microscopy using FITC-lectins and in electron microscopy revealed a disorganized endocyst and a reduction of the intercystic space area after cellulase treatment, implying that these cellular events are preliminary to trophozoite release during excystment. Further studies would be necessary to determine the signaling pathways involved during this amoebal differentiation process to identify new therapeutic targets for the development of anti-acanthamoebal drugs.

ABSTRACT Pneumocystis species are obligate fungal biotrophs that colonize the lungs of mammals. They cause deadly pneumonia in immunocompromised hosts. The sexual phase seems obligate during their life cycle and essential for survival because it is believed to ensure proliferation and transmission between hosts. Here, we consider if the sexual phase is initiated by the fusion of two cells or by nucleus duplication in order to generate diploid cells that can undergo meiosis. The juxtaposition of the nucleus-associated organelles of pairs of cells with fused cytoplasmic membranes demonstrated that cell fusion can occur. Nevertheless, the frequency of cell fusion remains to be determined, and it cannot be excluded that both cell fusion and nucleus duplication are used to ensure the occurrence of the essential sexual phase. In vitro culturing of these fungi is a major milestone that could clarify the issue.

One of the most distinctive characteristics of archaea is their unique lipids. While the general nature of archaeal lipids has been linked to their tolerance to extreme conditions, little is known about the diversity of lipidic structures archaea are able to synthesize, which hinders the elucidation of the physicochemical properties of their cell membrane. In an effort to widen the known lipid repertoire of the piezophilic and hyperthermophilic model archaeon Thermococcus barophilus, we comprehensively characterized its intact polar lipid (IPL), core lipid (CL), and polar head group compositions using a combination of cutting-edge liquid chromatography and mass spectrometric ionization systems. We tentatively identified 82 different IPLs based on five distinct CLs and 10 polar head group derivatives of phosphatidylhexoses, including compounds reported here for the first time, e.g., di-N-acetylhexosamine phosphatidylhexose-bearing lipids. Despite having extended the knowledge on the lipidome, our results also indicate that the majority of T. barophilus lipids remain inaccessible to current analytical procedures and that improvements in lipid extraction and analysis are still required. This expanded yet incomplete lipidome nonetheless opens new avenues for understanding the physiology, physicochemical properties, and organization of the membrane in this archaeon as well as other archaea.

ZIF-8 and ZIF-67 containing various percentages of copper were successfully synthesized through a green in-situ thermal (IST) approach based on 2-methylimidazole (2-MIM) as the organic linker. The IST method has several advantages over previously reported studies, including solvent and additive-free reaction conditions, a mild reaction temperature, a single-step procedure, no activation requirements, and the use of the smallest precursor ratio (M/L). The high catalytic performance of Cu/ZIF-8 and Cu/ZIF-67 in click chemistry is attributed to their high specific surface area, excellent porosity, and structural stability. To achieve these features, a range of parameters—such as time, temperature, gas atmosphere, and precursor ratio—were optimized. Several characterization methods were used to confirm the features of the produced catalysts. Overall, the synthesis strategy for achieving the targeted ZIFs with unique features is “green” and does not require further activation or treatment to eliminate side products. This method has great potential for manufacturing metal-organic frameworks on a large scale. Moreover, water was used as a solvent during the click reaction, resulting in high yields and making this an attractive, green, and eco-friendly procedure.

COVID-19 vaccination raised concerns about its potential effects on physical performance. To assess the impact of COVID-19 vaccination on the perceived change in physical performance, we conducted an online survey among elite athletes from Belgium, Canada, France and Luxembourg, with questions about socio-demographics, COVID-19 vaccination, perceived impact on physical performance and perceived pressure to get vaccinated. Full vaccination was defined as two doses of mRNA or vector vaccine or a heterologous vaccine scheme. Among 1106 eligible athletes contacted, 306 athletes answered the survey and were included in this study. Of these, 72% perceived no change in their physical performance, 4% an improvement and 24% a negative impact following full COVID-19 vaccination. For 82% of the included athletes, the duration of the negative vaccine reactions was ≤3 days. After adjustment for potential confounding variables, practicing an individual sport, a duration of vaccine reactions longer than 3 days, a high level of vaccine reaction and the perceived pressure to get vaccinated were independently associated with a perceived negative impact on physical performance of more than 3 days after the vaccination. The perceived pressure to get vaccinated appears to be a parameter associated with the negative perceived change in the physical performance and deserves further consideration.

By studying the properties of a synthetic membrane mimicking an archaeal membrane and containing the apolar polyisoprenoid squalane, Salvador-Castell et al. show that lipid bilayer stability and functionality are shifted to higher temperatures under high pressure. These findings support the view that apolar lipids may constitute an adaptative route to high-temperature tolerance in archaeal hyperthermophiles.

Abstract Introduction Rickets is not an unusual diagnosis for pediatricians even currently in developed countries. Children typically present with leg bowing, enlargement of wrists, rachitic rosary (swelling of costochondral junctions) and/or waddling gait. But not every child with growth delay and enlarged metaphyses is diagnosed with rickets. Metaphyseal anadysplasia (MAD) is a disorder of variable severity with metaphyseal flaring and irregularities, without vertebral abnormalities. MAD is characterized by an early onset and a regressive course in late childhood without treatment, despite persistent short stature. Autosomal dominant or recessive variants in the matrix metalloproteinase 13 gene (MMP13) are responsible for these transient metaphyseal changes. Case presentation We report a new pathogenic heterozygous variant in MMP13 (NM_002427.4: c.216G>C, p.Gln72His) in a toddler, initially thought to have rickets, and his father, with MAD phenotypes. Additionally, we review the seven reported MMP13 variants. Conclusion One should keep a wide differential diagnosis in cases of suspected rickets, including skeletal dysplasias which might have a regressive course.

Abstract Free‐living amoebae (FLAs) are protozoa developing autonomously in diverse natural or artificial environments. The FLAs Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri represent a risk for human health as they can become pathogenic and cause severe cerebral infections, named granulomatous amoebic encephalitis (GAE), Balamuthia amoebic encephalitis (BAE), and primary amoebic meningoencephalitis (PAM), respectively. Additionally, Acanthamoeba sp. can also rarely disseminate to diverse organs, such as the skin, sinuses, or bones, and cause extracerebral disseminated acanthamebiasis (EDA). No consensus treatment has been established for cerebral FLA infections or EDA. The therapy of cerebral and disseminated FLA infections often empirically associates a large diversity of drugs, all exhibiting a high toxicity. Nevertheless, these pathologies lead to a high mortality, above 90% of the cases, even in the presence of a treatment. In the present work, a total of 474 clinical cases of FLA infections gathered from the literature allowed to determine the frequency of usage, as well as the efficacy of the main drugs and drug combinations used in the treatment of these pathologies. The efficacy of drug usage was determined based on the survival rate after drug administration. The most efficient drugs, drug combinations, and their mechanism of action were discussed in regard to the present recommendations for the treatment of GAE, EDA, BAE, and PAM. At the end, this review aims to provide a useful tool for physicians in their choice to optimize the treatment of FLA infections.

Arthrogryposis is a clinical feature defined by congenital joint contractures in two or more different body areas which occurs in between 1/3000 and 1/5000 live births. Variants in multiple genes have been associated with distal arthrogryposis syndromes. Heterozygous variants in MYH3 have been identified to cause the dominantly‐inherited distal arthrogryposis conditions, Freeman–Sheldon syndrome, Sheldon–Hall syndrome, and multiple pterygium syndrome. In contrast, MYH3 variants underlie both dominantly and recessively inherited Contractures, Pterygia, and Spondylocarpotarsal Fusion syndromes (CPSFS) which are characterized by extensive bony abnormalities in addition to congenital contractures. Here we report two affected sibs with distal arthrogryposis born to unaffected, distantly related parents. Sequencing revealed that both sibs were homozygous for two ultra‐rare MYH3 variants, c.3445G>A (p.Glu1149Lys) and c.4760T>C (p.Leu1587Pro). Sequencing and deletion/duplication analysis of 169 other arthrogryposis genes yielded no other compelling candidate variants. This is the first report of biallelic variants in MYH3 being implicated in a distal arthrogryposis phenotype without the additional features of CPSFS. Thus, akin to CPSFS, both dominant and recessively inherited distal arthrogryposis can be caused by variants in MYH3. [ABSTRACT FROM AUTHOR]

In approximately one decade, global temperatures will likely exceed a warming level that a United Nations Intergovernmental Panel on Climate Change report considers a "red alert for humanity". We propose exploring tidal flat diatoms to address climate change challenges. Tidal flats are extensive coastal ecosystems crucial to the provisioning and regulation of aquatic environments. Diatoms contribute to tidal flat biomass production and account for 20% of global primary productivity and 40% of annual marine biomass production, making them crucial for nutrient cycling and sediment stabilization. Potential CO2 removal from Korean tidal flats by diatoms is estimated to be 598,457–683,171 t CO2 equivalents (CO2e) annually, with the economic value of blue carbon (BC) resulting from diatom activity being approximately US$ 17.95–20.50 million. Dissemination of this potential could incentivize coastal wetland protection and climate change mitigation measures. The global estimated CO2e removal potential of tidal flat diatoms is 40,957,346–46,754,961 t CO2e, representing 0.11–0.13% of the annual global greenhouse gas emissions, even though tidal flats cover 0.0025% of the Earth's surface and diatoms represent less than 0.5% (by weight) of all photosynthetic plants. Researchers should combine ecology and economics to develop standardized approaches for carbon input monitoring and quantification. Further, spatiotemporal analyses of environmental threats to tidal flat diatoms are necessary for conserving their biodiversity and function as a critical BC source. Land-based cultivation for large-scale biomass production and biorefinery processes can contribute to a greener, more prosperous future for humanity and the marine ecosystems upon which we rely. [ABSTRACT FROM AUTHOR]

The eukaryotic CDC45/MCM2-7/GINS (CMG) helicase unwinds the DNA double helix during DNA replication. The GINS subcomplex is required for helicase activity and is, therefore, essential for DNA replication and cell viability. Here, we report the identification of 7 individuals from 5 unrelated families presenting with a Meier-Gorlin syndrome–like (MGS-like) phenotype associated with hypomorphic variants of GINS3, a gene not previously associated with this syndrome. We found that MGS-associated GINS3 variants affecting aspartic acid 24 (D24) compromised cell proliferation and caused accumulation of cells in S phase. These variants shortened the protein half-life, altered key protein interactions at the replisome, and negatively influenced DNA replication fork progression. Yeast expressing MGS-associated variants of PSF3 (the yeast GINS3 ortholog) also displayed impaired growth, S phase progression defects, and decreased Psf3 protein stability. We further showed that mouse embryos homozygous for a D24 variant presented intrauterine growth retardation and did not survive to birth, and that fibroblasts derived from these embryos displayed accelerated cellular senescence. Taken together, our findings implicate GINS3 in the pathogenesis of MGS and support the notion that hypomorphic variants identified in this gene impaired cell and organismal growth by compromising DNA replication.

Chalcones (1,3-diphenyl-2-propen-1-ones) either natural or synthetic have a plethora of biological properties including antileishmanial activities, but their development as drugs is hampered by their largely unknown mechanisms of action. We demonstrate herein that our previously described benzochalcone fluorogenic probe (HAB) could be imaged by fluorescence microscopy in live Leishmania amazonensis promastigotes where it targeted the parasite acidocalcisomes, lysosomes and the mitochondrion. As in the live zebrafish model, HAB formed yellow-emitting fluorescent complexes when associated with biological targets in Leishmania. Further, we used HAB as a reversible probe to study the binding of a portfolio of diverse chalcones and analogues in live promastigotes, using a combination of competitive flow cytometry analysis and cell microscopy. This pharmacological evaluation suggested that the binding of HAB in promastigotes was representative of chalcone pharmacology in Leishmania, with certain exogenous chalcones exhibiting competitive inhibition (ca. 20–30%) towards HAB whereas non-chalconic inhibitors showed weak capacity (ca. 3–5%) to block the probe intracellular binding. However, this methodology was restricted by the strong toxicity of several competing chalcones at high concentration, in conjunction with the limited sensitivity of the HAB fluorophore. This advocates for further optimization of this undirect target detection strategy using pharmacophore-derived reversible fluorescent probes.

Lipid membranes are a key component of living systems and have been essential to the origin of life. One hypothesis for the origin of life assumes the existence of protomembranes with ancient lipids formed by Fischer–Tropsch synthesis. We determined the mesophase structure and fluidity of a prototypical decanoic (capric) acid-based system, a fatty acid with a chain length of 10 carbons, and a lipid system consisting of a 1:1 mixture of capric acid with a fatty alcohol of equal chain length (C10 mix). To shed light on the mesophase behavior and fluidity of these prebiotic model membranes, we employed Laurdan fluorescence spectroscopy, which reports on the lipid packing and fluidity of membranes, supplemented by small-angle neutron diffraction data. The data are compared with data of the corresponding phospholipid bilayer systems of the same chain length, 1,2-didecanoyl-sn-glycero-3-phosphocholine (DLPC). We demonstrate that the prebiotic model membranes capric acid and the C10 mix show formation of stable vesicular structures needed for cellular compartmentalization at low temperatures only, typically below 20 °C. They reveal the fluid-like lipid dynamic properties needed for optimal physiological function. High temperatures lead to the destabilization of the lipid vesicles and the formation of micellar structures.

The potential benefits of microwave irradiation for fructose dehydration into 5 hydroxymethylfurfural (5-HMF) have been quantified over a sulfonated metal–organic framework (MOF), MIL 101(Cr)-SO3H. The effects of temperature (140–170 °C), batch time (5–300 min), and catalyst-to-substrate ratio (0.1–0.01 g/g) were systematically mapped. After 10 min of microwave (MW) irradiation at 140 °C in a DMSO–acetone reaction medium, practically complete fructose conversion was obtained with a 70% yield of 5-HMF. Without MW, i.e., using conventional heating (CH) at the same conditions, the fructose conversion was limited to 13% without any 5-HMF yield. Rather, 90 min of CH was required to reach a similarly high conversion and yield. The profound impact of moving from CH towards MW conditions on the reaction kinetics, also denoted as the microwave effect, has been quantified through kinetic modeling via a change in the Gibbs free energy of the transition state. The modeling results revealed an eight-fold rate coefficient enhancement for fructose dehydration owing to MW irradiation, while the temperature dependence of the various reaction steps almost completely disappeared in the investigated range of operating conditions.

The development of water‐based composite cathode slurries for Li‐ion batteries is hindered by adverse interactions between the battery active material and water. Insights into interactions between H2O and LiNi0.5Mn1.5O4 (LNMO) are studied using a thin‐film model system. The reactivity of this active material with H2O is evaluated at different lithiation states, showing that protonation of the active material in aqueous environments is electrochemically driven, rather than a chemical Li+/H+ ion exchange reaction. The electrochemically driven mechanism describing the protonation of LNMO is only present when the material is in its partially delithiated form. These findings suggest it is possible to cast this material from an aqueous precursor when lithiated, as long as there are no traces of it when the electrochemical delithiation (cell charging) is carried out. [ABSTRACT FROM AUTHOR]

Saline-alkaline lakes often shelter high biomasses despite challenging conditions, owing to the occurrence of highly adapted phototrophs. Dziani Dzaha (Mayotte) is one such lake characterized by the stable co-dominance of the cyanobacterium Limnospira platensis and the picoeukaryote Picocystis salinarum throughout its water column. Despite light penetrating only into the uppermost meter, the prevailing co-dominance of these species persists even in light- and oxygen-deprived zones. Here, a depth profile of phototrophs metatranscriptomes, annotated using genomic data from isolated strains, is employed to identify expression patterns of genes related to carbon processing pathways including photosynthesis, transporters and fermentation. The findings indicate a prominence of gene expression associated with photosynthesis, with a peak of expression around 1 m below the surface, although the light intensity is very low and only red and dark red wavelengths can reach it, given the very high turbidity linked to the high biomass of L. platensis. Experiments on strains confirmed that both species do grow under these wavelengths, at rates comparable to those obtained under white light. A decrease in the expression of photosynthesis-related genes was observed in L. platensis with increasing depth, whereas P. salinarum maintained a very high pool of psbA transcripts down to the deepest point as a possible adaptation against photodamage, in the absence and/or very low levels of expression of genes involved in protection. In the aphotic/anoxic zone, expression of genes involved in fermentation pathways suggests active metabolism of reserve or available dissolved carbon compounds. Overall, L. platensis seems to be adapted to the uppermost water layer, where it is probably maintained thanks to gas vesicles, as evidenced by high expression of the gvpA gene. In contrast, P. salinarum occurs at similar densities throughout the water column, with a peak in abundance and gene expression levels which suggests a better adaptation to lower light intensities. These slight differences may contribute to limited inter-specific competition, favoring stable co-dominance of these two phototrophs. [ABSTRACT FROM AUTHOR]

Point‐of‐care (POC) devices require more advanced detection techniques than those currently available to achieve enhanced quantification and sensitivity. Incorporating a micro power supply could be a viable solution to enable the implementation of these techniques. In recent years, paper‐based microfluidic galvanic cells (μGCs) have emerged as promising disposable power sources; however, the fabrication process remains labor intensive. This study demonstrates the potential of three‐dimensional printing as a novel fabrication method for μGCs. The autonomous μGCs are fabricated using a powder‐based 3DPed method, resulting in a porous body in which capillary forces enable the coflow of redox‐active solutions. As a proof of concept, a handheld glucometer is powered by coupling four μGCs in series. [ABSTRACT FROM AUTHOR]

Tatton–Brown–Rahman syndrome (TBRS) is a rare autosomal dominant overgrowth syndrome first reported in 2014 and caused by pathogenic variants in the DNA methyltransferase 3A (DNMT3A) gene. All individuals reported to date share a phenotype of somatic overgrowth, dysmorphic features, and intellectual disability. Peripheral neuropathy was not described in these cases. We report an adult patient with TBRS caused by a novel pathogenic DNMT3A variant (NM_175629.2: c.2036G>A, p.(Arg688His)) harboring an axonal length‐dependent sensory‐motor polyneuropathy. Extensive laboratory and molecular genetic work‐up failed to identify alternative causes for this patient's neuropathy. We propose that axonal neuropathy may be a novel, age‐dependent phenotypic feature in adults with TBRS and suggest that this syndrome should be considered in the differential diagnosis of patients with overgrowth, cognitive and psychiatric difficulties, and peripheral neuropathy. [ABSTRACT FROM AUTHOR]

2,6-Diaryl-4H-tetrahydro-thiopyran-4-ones and corresponding sulfoxide and sulfone derivatives were designed to lower the major toxicity of their parent anti-kinetoplatidal diarylideneacetones through a prodrug effect. Novel diastereoselective methodologies were developed and generalized from diarylideneacetones and 2,6-diaryl-4H-tetrahydro-thiopyran-4-ones to allow the introduction of a wide substitution profile and to prepare the related S-oxides. The in vitro biological activity and selectivity of diarylideneacetones, 2,6-diaryl-4H-tetrahydro-thiopyran-4-ones, and their S-sulfoxide and sulfone metabolites were evaluated against Trypanosoma brucei brucei, Trypanosoma cruzi, and various Leishmania species in comparison with their cytotoxicity against human fibroblasts hMRC-5. The data revealed that the sulfides, sulfoxides, and sulfones, in which the Michael acceptor sites are temporarily masked, are less toxic against mammal cells while the anti-trypanosomal potency was maintained against T. b. brucei, T. cruzi, L. infantum, and L. donovani, thus confirming the validity of the prodrug strategy. The mechanism of action is proposed to be due to the involvement of diarylideneacetones in cascades of redox reactions involving the trypanothione system. After Michael addition of the dithiol to the double bonds, resulting in an elongated polymer, the latter—upon S-oxidation, followed by syn-eliminations—fragments, under continuous release of reactive oxygen species and sulfenic/sulfonic species, causing the death of the trypanosomal parasites in the micromolar or submicromolar range with high selectivity indexes. [ABSTRACT FROM AUTHOR]

Abstract Purpose Anterior cruciate ligament (ACL) rupture is a common injury and psychological parameters measured at 6–8 months are said to be almost more predictive for return to sport (RTS) than physiological. Purpose was 1) to evaluate the correlation between knee apprehension using ACL‐RSI and physical factors after ACL reconstruction (ACLR), 2) to assess the correlation between ACL‐RSI and patient parameters (age, pivot‐sport, BMI), and 3) to evaluate ACL‐RSI over time. Methods Patients with ACLR with or without meniscal repair between 2013 and 2020 were retrospectively analyzed. Including criteria were RTS testing battery, assessed at least 6 months after surgery, including physical parameters (strength, triple hop test, side hop test, and bilateral knee stability) and psychological parameters (ACL‐RSI). 5 subgroups were analyzed to assessed factors such as age, BMI, pivot sport, time interval between two RTS testing battery. Results Three hundred three patients (212 male, 91 female) presenting ACLR were included. Mean age at surgery was 27 (± 8) years. 258 patients practiced pivot‐sport activity and 45 non‐pivot‐sport activity. The mean interval between ACL rupture and surgery was 6.5 (± 4.5) months. RTS testing battery were performed at 8 (± 7) months after ACLR. Mean ACL‐RSI was 58 (± 28). 1) ACL‐RSI was not influenced by muscle strength, coordination and stability of the knee. 2) ACL‐RSI was significantly better in lower BMI and non‐pivot‐sport activities. No correlation was found between graft type, age, sex, and ACL‐RSI assessment. 3) For patients who performed two RTS testing battery at 8 and 12 months, ACL‐RSI did not significantly increase over time (56 to 64 points, p = 0.22) in spite of significant increased quadriceps (127 to 151 Nm/kg, p = 0.005) and hamstring (93 to 105 Nm/kg, p = 0.05) strength. Conclusions Psychological readiness before RTS, measured upon ACL‐RSI does not correlate with any physical parameter at 8–12 months postoperatively. Although quadriceps and hamstring strength increased significantly over time, ACL‐RSI does not and must therefore be routinely assessed.

Summary: Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes. We demonstrate increasing resolution and specificity ranging from protein complex, gene, sub-gene, protein domain, and even single nucleotide-level Mendelian episignatures. We show the power of multiclass modeling to develop highly accurate and disease-specific diagnostic classifiers. This study significantly expands the number and spectrum of disorders with detectable DNA methylation episignatures, improves the clinical diagnostic capabilities through the resolution of unsolved cases and the reclassification of variants of unknown clinical significance, and provides further insight into the molecular etiology of Mendelian conditions.

Abstract Background Osteochondritis dissecans is a condition wherein there is a subchondral bone lesion that causes pain, inflammation, and cartilage damage. Dominant Familial Osteochondritis Dissecans is a rare and severe form of osteochondritis dissecans (OCD). It is caused by heterozygous pathogenic variants in the gene encoding Aggrecan; ACAN. Aggrecan, a proteoglycan, is an essential component of the articular and growth plate cartilage. Methods Herein, we report three individuals from one family; the proband who presented with short stature, a lower limb bone exostosis, and bilateral knee and elbow OCD at the age of 13 years old. His twin brother presented with isolated short stature and his father with short stature and lumbar disc herniation. Results Next‐generation sequencing of the ACAN gene in the proband identified a frameshift variant which is also present in the brother and father with short stature. The proband was treated surgically with bilateral elbow microfracture, after the failure of conservative therapy. Conclusion To the best of our knowledge, this is the first patient with an aggrecanopathy who presents with osteochondritis dissecans due to a frameshift variant. This family presents with variable expressivity which might be attributed to modifier genes.