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Nature Genetics Jan 1996
Topics: Achondroplasia; Anion Transport Proteins; Carrier Proteins; Cartilage; Female; Humans; Male; Membrane Transport Proteins; Point Mutation; Proteoglycans; Sequence Deletion; Sulfate Transporters; Sulfates
PubMed: 8528239
DOI: 10.1038/ng0196-100 -
American Journal of Medical Genetics.... Apr 2020We present two unrelated Japanese pedigrees with achondrogenesis type 1b (ACG1B), characterized by prenatally lethal fetal hydrops and severe micromelia. The affected...
We present two unrelated Japanese pedigrees with achondrogenesis type 1b (ACG1B), characterized by prenatally lethal fetal hydrops and severe micromelia. The affected members in these pedigrees carried a common homozygous missense point mutation in solute carrier family 26 member 2 (SLC26A2), a gene associated with ACG1B (NM_000112:c.1987G>A). This loss-of-function point mutation causes substitution of glycine 663 with arginine in a highly conserved loop domain of SLC26A2. Interestingly, only a few cases of this mutation have been registered in Japanese genomic databases, and there are no reports of this mutation in any major genomic databases outside Japan. Furthermore, we confirmed the presence of a homozygous stretch of approximately 75 kb surrounding the pathogenic variant. Our findings suggest that this missense point mutation in SLC26A2, which is likely the cause of the ACG1B phenotypes in these unrelated fetuses, is distributed exclusively in Japan.
Topics: Achondroplasia; Adult; Female; Humans; Japan; Male; Mutation; Pedigree; Phenotype; Sulfate Transporters
PubMed: 31880411
DOI: 10.1002/ajmg.a.61469 -
European Journal of Pediatrics Jun 1980The light- and electron-microscopic structure of articular and costal cartilage in a case of achondrogenesis type I has been described. The most characteristic...
The light- and electron-microscopic structure of articular and costal cartilage in a case of achondrogenesis type I has been described. The most characteristic ultrastructural change in the chondrocytes was conspicuous dilatation of the rough endoplasmatic reticulum (RER) which contained amorphous electronopaque material. This change in the RER was accompanied by marked hypertrophy of the Golgi apparatus; the matrix was basically unchanged.
Topics: Achondroplasia; Autopsy; Cartilage, Articular; Endoplasmic Reticulum; Female; Golgi Apparatus; Humans; Hypertrophy; Inclusion Bodies; Infant, Newborn; Microscopy, Electron
PubMed: 6250850
DOI: 10.1007/BF00442406 -
Radiology Sep 1983Achondrogenesis is a phenotypically diverse group of lethal osteochondrodysplasias characterized by severe micromelia, a short trunk, and a disproportionately large...
Achondrogenesis is a phenotypically diverse group of lethal osteochondrodysplasias characterized by severe micromelia, a short trunk, and a disproportionately large cranium. Cases of classic achondrogenesis Type I (Parenti-Fraccaro), and classic achondrogenesis Type II (Langer-Saldino) have been grouped on the basis of clinical, radiologic, and histopathologic features. Although further genetic heterogeneity has been proposed, broad acceptance has been lacking. Review of 79 cases, including examination of available radiographs of familial cases, permitted division into four radiographic prototypes. Cases were distinguished on the basis of specific skeletal features as well as a new parameter, the "femoral cylinder index" (CIfemur). Using these criteria, the affected siblings in 11 families were found to be concordant for prototype. Thus, identification of radiographic skeletal prototypes of achondrogenesis, and the observation of familial concordance for prototype, suggested the existence of at least four genetically distinct disorders, each having autosomal recessive transmission. These observations should provide further impetus for histopathologic and biochemical studies of the defects in achondrogenesis.
Topics: Achondroplasia; Extremities; Femur; Gestational Age; Humans; Infant, Newborn; Osteochondrodysplasias; Pedigree; Radiography
PubMed: 6878687
DOI: 10.1148/radiology.148.3.6878687 -
Nutrients Mar 2015Sulphate is an obligate nutrient for healthy growth and development. Sulphate conjugation (sulphonation) of proteoglycans maintains the structure and function of... (Review)
Review
Sulphate is an obligate nutrient for healthy growth and development. Sulphate conjugation (sulphonation) of proteoglycans maintains the structure and function of tissues. Sulphonation also regulates the bioactivity of steroids, thyroid hormone, bile acids, catecholamines and cholecystokinin, and detoxifies certain xenobiotics and pharmacological drugs. In adults and children, sulphate is obtained from the diet and from the intracellular metabolism of sulphur-containing amino acids. Dietary sulphate intake can vary greatly and is dependent on the type of food consumed and source of drinking water. Once ingested, sulphate is absorbed into circulation where its level is maintained at approximately 300 μmol/L, making sulphate the fourth most abundant anion in plasma. In pregnant women, circulating sulphate concentrations increase by twofold with levels peaking in late gestation. This increased sulphataemia, which is mediated by up-regulation of sulphate reabsorption in the maternal kidneys, provides a reservoir of sulphate to meet the gestational needs of the developing foetus. The foetus has negligible capacity to generate sulphate and thereby, is completely reliant on sulphate supply from the maternal circulation. Maternal hyposulphataemia leads to foetal sulphate deficiency and late gestational foetal death in mice. In humans, reduced sulphonation capacity has been linked to skeletal dysplasias, ranging from the mildest form, multiple epiphyseal dysplasia, to achondrogenesis Type IB, which results in severe skeletal underdevelopment and death in utero or shortly after birth. Despite being essential for numerous cellular and metabolic functions, the nutrient sulphate is largely unappreciated in clinical settings. This article will review the physiological roles and regulation of sulphate during pregnancy, with a particular focus on animal models of disturbed sulphate homeostasis and links to human pathophysiology.
Topics: Amino Acids, Sulfur; Animals; Deficiency Diseases; Diet; Female; Fetal Development; Humans; Pregnancy; Pregnancy Complications; Prenatal Nutritional Physiological Phenomena; Sulfates
PubMed: 25746011
DOI: 10.3390/nu7031594 -
Clinical Dysmorphology Jul 2008
Topics: Abnormalities, Multiple; Achondroplasia; Bone and Bones; Female; Hamartoma; Humans; Infant, Newborn; Premature Birth; Radiography; Skin Diseases; Stillbirth
PubMed: 18541971
DOI: 10.1097/MCD.0b013e328300595c -
American Journal of Medical Genetics.... Oct 2013Achondrogenesis 1A (ACG1A; OMIM 200600) is an autosomal recessive perinatally lethal skeletal dysplasia comprising intrauterine growth failure, micromelia, minor facial...
Achondrogenesis 1A (ACG1A; OMIM 200600) is an autosomal recessive perinatally lethal skeletal dysplasia comprising intrauterine growth failure, micromelia, minor facial anomalies, deficient ossification of the skull, absent or extremely defective spinal ossification, short beaded ribs, and short deformed long bones with a stellate appearance. ACG1A is caused by mutations in the TRIP11 gene, resulting in deficiency of the Golgi microtubule associated protein 210. In this study we describe dizygotic twins with a clinical and radiological phenotype of ACG1A who were homozygous for a novel nonsense mutation in the TRIP11 gene. In addition, another patient with a milder manifestation, not readily distinguishable from those of other lethal skeletal dysplasias, was found to be a compound heterozygote for a nonsense mutation and a deletion of the 3' end of the TRIP11 gene. We conclude that mutations of the TRIP11 gene may encompass a wider phenotypic range than previously recognized.
Topics: Achondroplasia; Cytoskeletal Proteins; Diagnostic Imaging; Female; Genotype; Humans; Infant, Newborn; Male; Mutation; Nuclear Proteins; Phenotype; Twins, Dizygotic
PubMed: 23956106
DOI: 10.1002/ajmg.a.36106 -
Development (Cambridge, England) Jan 2018Inactivating mutations in the ubiquitously expressed membrane trafficking component GMAP-210 (encoded by ) cause achondrogenesis type 1A (ACG1A). ACG1A is surprisingly...
Inactivating mutations in the ubiquitously expressed membrane trafficking component GMAP-210 (encoded by ) cause achondrogenesis type 1A (ACG1A). ACG1A is surprisingly tissue specific, mainly affecting cartilage development. Bone development is also abnormal, but as chondrogenesis and osteogenesis are closely coupled, this could be a secondary consequence of the cartilage defect. A possible explanation for the tissue specificity of ACG1A is that cartilage and bone are highly secretory tissues with a high use of the membrane trafficking machinery. The perinatal lethality of ACG1A prevents investigating this hypothesis. We therefore generated mice with conditional knockout alleles and inactivated in chondrocytes, osteoblasts, osteoclasts and pancreas acinar cells, all highly secretory cell types. We discovered that the ACG1A skeletal phenotype is solely due to absence of GMAP-210 in chondrocytes. Mice lacking GMAP-210 in osteoblasts, osteoclasts and acinar cells were normal. When we inactivated in primary chondrocyte cultures, GMAP-210 deficiency affected trafficking of a subset of chondrocyte-expressed proteins rather than globally impairing membrane trafficking. Thus, GMAP-210 is essential for trafficking specific cargoes in chondrocytes but is dispensable in other highly secretory cells.
Topics: Achondroplasia; Alleles; Animals; Biological Transport, Active; Bone Development; Cartilage; Chondrocytes; Cytoskeletal Proteins; Mice; Mice, Knockout; Nuclear Proteins; Osteoblasts; Osteoclasts; Phenotype
PubMed: 29180569
DOI: 10.1242/dev.156588 -
Anales Espanoles de Pediatria Dec 2001We present a case of lethal dysplasia in the neonatal period. The abnormality was suspected after ultrasonography of a pregnant woman presenting weak fetal movements...
We present a case of lethal dysplasia in the neonatal period. The abnormality was suspected after ultrasonography of a pregnant woman presenting weak fetal movements revealed shortening of the extremities, voluminous cranium and polyhydramnios. Clinical and radiological findings showed platyspondylic dwarfism with short extremities, narrow thorax and hydropic appearance. The infant died on the third day of life from progressive respiratory distress. In the absence of histological, chondro-osseus and molecular studies, detailed clinical and radiological studies, as well as the lethal evolution during the neonatal period, guided the diagnosis of hypochondrogenesis. This entity, together with achondrogenesis II (and other dysplasias), forms part of the same spectrum of collagen type II abnormalities produced by a defect in the gene (COL2A1) that codifies collagen II, located in chromosome 12 I(12q13.1-13.2). When a heterozygote is produced, transmission is dominant autosomal. The phenotype shows wide variation and severity depends on the mechanism and location of the mutation. The definitive diagnosis is given by cytomolecular studies, while individualization of the different entities is based on histological data from the cartilage; clinical findings and skeletal radiology serve as a guide.
Topics: Chromosomes, Human, Pair 12; Collagen Type II; Fatal Outcome; Female; Humans; Infant, Newborn; Osteochondrodysplasias; Radiography
PubMed: 11730591
DOI: No ID Found