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Clinical Genetics Sep 2023The GNAS locus is an imprinted site. The α-subunit of the stimulatory G protein (Gsα) and extralarge variant (XLαs) are the two important products of the GNAS locus.... (Review)
Review
The GNAS locus is an imprinted site. The α-subunit of the stimulatory G protein (Gsα) and extralarge variant (XLαs) are the two important products of the GNAS locus. The abnormal expression of Gsα is associated with pseudohypoparathyroidism (PHP) and related disorders, including Albright hereditary osteodystrophy (AHO), pseudopseudohypoparathyroidism (PPHP), and progressive osseous heteroplasia (POH). XLαs protein can mimic the catalytic intracellular synthesis of cyclic adenosine monophosphate (cAMP) by Gsα in response to parathyroid hormone (PTH) stimulation, which may be involved in the pathogenesis of PPHP and POH in patients with paternal GNAS defects. A paternally inherited nonsense variant in the first exon of XLαs in an adult patient may be associated with fractures and osteopetrosis. The relationship between the XLαs product of the GNAS locus and bone remodeling may have been overlooked. Here, we summarize the phenotypes of genetic mouse models and clinical cases of XLαs variations and suggest that the abnormal paternal expression of XLαs may be associated with the development of POH and affect osteoblast and osteoclast differentiation.
Topics: Humans; Animals; Mice; Bone Density; Chromogranins; GTP-Binding Protein alpha Subunits, Gs; Pseudohypoparathyroidism; Mutation
PubMed: 37249323
DOI: 10.1111/cge.14378 -
Skin Research and Technology : Official... Nov 2023
Topics: Humans; Skin Diseases, Genetic; Ossification, Heterotopic; Bone Diseases, Metabolic; Skin Neoplasms
PubMed: 38009037
DOI: 10.1111/srt.13510 -
QJM : Monthly Journal of the... Jun 2024
Topics: Humans; Pseudohypoparathyroidism; Skin Diseases, Genetic; Ossification, Heterotopic; Female; Male; Bone Diseases, Metabolic
PubMed: 38265255
DOI: 10.1093/qjmed/hcae017 -
Journal of Cutaneous Pathology Dec 2023
Topics: Humans; Skin Diseases, Genetic; Bone Diseases, Metabolic; Ossification, Heterotopic; Skin Neoplasms
PubMed: 37743717
DOI: 10.1111/cup.14537 -
Annals of Dermatology Nov 2023
PubMed: 38061755
DOI: 10.5021/ad.22.120 -
Cureus Sep 2023Background In this study, we aimed to determine the prevalence and radiographic features of incidental head and neck soft tissue calcifications (STCs) on panoramic...
Background In this study, we aimed to determine the prevalence and radiographic features of incidental head and neck soft tissue calcifications (STCs) on panoramic imagesand assess their clinical significance. Methodology Following well-established training and calibration procedures, 9,553 digital panoramic radiographs (DPRs) taken between January 1, 2021, and January 31, 22, were retrospectively evaluated. Only obvious calcifications and clear differential diagnoses were considered. The presence, type, side (i.e., unilateral or bilateral), number (single or multiple), and the presence of different calcifications in the same individual were recorded. STCs were recorded according to age and gender. Data were analyzed using the chi-square test and Fisher's exact test using SPSS version 18.0 (IBM Corp., Armonk, NY, USA). Results Overall, 35.8% of the DPRs studied showed the presence of STCs, including ossified stylohyoid complex (OSHC) (10.3%), thyroid cartilage (9.8%), tonsillolith (9.2%), atherosclerotic plaques (5.8%), calcified triticeous cartilage (CTC) (5.1%), sialolith (1.9%), as well as intra-articular (1.3%) and other calcifications (0.1-0.8%), i.e., calcified lymph node, antrolith, rhinolith, phlebolith, and osteoma cutis. STCs were found to be more prevalent in middle-aged patients and in females. A significant relationship was identified between the presence of carotid artery calcification and calcified superior horn of thyroid cartilage (CSHTC), as well as between the presence of CSHTC and CTC. Calcifications were detected either bilaterally (n = 2,003) or unilaterally (n = 2,388); however, OSHC mostly showed bilateral calcifications (8.5%). Conclusions Panoramic radiographs of dental patients reveal the frequent occurrence of STCs in the head and neck region with differing radiographic features. Certain calcifications show gender and age differences. Accurate detection of STCs may guide the identification of potential underlying diseases and help initiate referral to the relevant multidisciplinary teams.
PubMed: 37766776
DOI: 10.7759/cureus.46025 -
Journal of Pediatric Endocrinology &... May 2024Inactivating mutations result in varied phenotypes depending on parental origin. Maternally inherited mutations typically lead to hormone resistance and Albright's...
OBJECTIVES
Inactivating mutations result in varied phenotypes depending on parental origin. Maternally inherited mutations typically lead to hormone resistance and Albright's hereditary osteodystrophy (AHO), characterised by short stature, round facies, brachydactyly and subcutaneous ossifications. Paternal inheritance presents with features of AHO or ectopic ossification without hormone resistance. This report describes the case of a child with osteoma cutis and medulloblastoma. The objective of this report is to highlight the emerging association between inactivating germline mutations and medulloblastoma, aiming to shed light on its implications for tumor biology and promote future development of targeted surveillance strategies to improve outcomes in paediatric patients with these mutations.
CASE PRESENTATION
A 12-month-old boy presented with multiple plaque-like skin lesions. Biopsy confirmed osteoma cutis, prompting genetic testing which confirmed a heterozygous inactivating mutation. At 2.5 years of age, he developed neurological symptoms and was diagnosed with a desmoplastic nodular medulloblastoma, SHH molecular group, confirmed by MRI and histology. Further analysis indicated a biallelic loss of in the tumor.
CONCLUSIONS
This case provides important insights into the role of as a tumor suppressor and the emerging association between inactivating variants and the development of medulloblastoma. The case underscores the importance of careful neurological assessment and ongoing vigilance in children with known inactivating variants or associated phenotypes. Further work to establish genotype-phenotype correlations is needed to inform optimal management of these patients.
Topics: Humans; GTP-Binding Protein alpha Subunits, Gs; Male; Chromogranins; Medulloblastoma; Ossification, Heterotopic; Skin Diseases, Genetic; Infant; Cerebellar Neoplasms; Prognosis; Bone Diseases, Metabolic; Mutation
PubMed: 38529810
DOI: 10.1515/jpem-2023-0533 -
Medicina (Kaunas, Lithuania) Apr 2024Soft tissue calcifications frequently appear on imaging studies, representing a prevalent but non-specific discovery, varying from a local reaction without clear cause...
Soft tissue calcifications frequently appear on imaging studies, representing a prevalent but non-specific discovery, varying from a local reaction without clear cause to suggesting an underlying systemic condition. Because calcifications like these can arise from various causes, an accurate differential diagnosis is crucial. Differential diagnosis entails a methodical assessment of the patient, encompassing clinical presentation, medical history, radiological and pathological findings, and other pertinent factors. Through scrutiny of the patient's medical and trauma history, we can refine potential causes of calcification to vascular, metabolic, autoimmune, neoplastic, or traumatic origins. Furthermore, routine laboratory assessments, including serum levels of calcium, phosphorus, ionized calcium, vitamin D metabolites, and parathyroid hormone (PTH), aid in identifying metabolic etiologies. We describe a rare occurrence of osteoma cutis in a 15-year-old female patient with a history of pseudohypoparathyroidism (PHP) and Albright's hereditary osteodystrophy (AHO). The patient presented with a painful mass on the lateral side of her left foot. The diagnosis was based on medical history, laboratory tests, and imaging, leading to an excisional biopsy and complete pain relief post-surgery. Understanding such rare occurrences and related conditions is crucial for accurate diagnosis and management.
Topics: Humans; Female; Calcinosis; Pseudohypoparathyroidism; Adolescent; Diagnosis, Differential; Foot; Bone Diseases, Metabolic
PubMed: 38674241
DOI: 10.3390/medicina60040595 -
Veterinary Dermatology Jun 2024A climbing mantella frog (Mantella laevigata) was presented with nodular thickened skin. Histological examination revealed dermal nodules composed of differentiated bone...
A climbing mantella frog (Mantella laevigata) was presented with nodular thickened skin. Histological examination revealed dermal nodules composed of differentiated bone consistent with miliary osteoma cutis, a non-neoplastic condition where bone is abnormally deposited within the skin. This is the first report of idiopathic osteoma cutis in an amphibian.
PubMed: 38938127
DOI: 10.1111/vde.13273