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Human Genome Variation Nov 2022Achondrogenesis type II (ACG2) is a lethal skeletal disorder caused by pathogenic variants in COL2A1. We present a fetus with cystic hygroma and severe shortening of the...
Achondrogenesis type II (ACG2) is a lethal skeletal disorder caused by pathogenic variants in COL2A1. We present a fetus with cystic hygroma and severe shortening of the limbs at 14 weeks of gestation. We performed postnatal genetic analysis of the parents and fetus to diagnose the disease. A novel missense variant of COL2A1 [NM_001844.5: c.2987G>A, (p. Gly996Asp)] was identified, which led to the ACG2 diagnosis.
PubMed: 36376277
DOI: 10.1038/s41439-022-00218-5 -
The British Journal of Radiology Jan 1981
Topics: Bone and Bones; Chromosome Aberrations; Chromosome Disorders; Diagnosis, Differential; Diseases in Twins; Dwarfism; Female; Genes, Recessive; Humans; Infant, Newborn; Pregnancy; Radiography; Twins, Monozygotic
PubMed: 7192589
DOI: 10.1259/0007-1285-54-637-61 -
The Application of Clinical Genetics 2018Achondrogenesis type IA (ACG1A) is a rare, lethal autosomal recessive chondrodysplasia affecting endochondral bone ossification and differentiation, causing intrauterine...
BACKGROUND
Achondrogenesis type IA (ACG1A) is a rare, lethal autosomal recessive chondrodysplasia affecting endochondral bone ossification and differentiation, causing intrauterine growth restriction, narrow thorax, and short limbs. Mutations in , which encodes Golgi microtubule-binding protein 210 in the Golgi apparatus, alter protein transport in tissues.
CASE PRESENTATION
A 28-week gestation male fetus was diagnosed with ACG1A by clinical, radiological, histologic, and molecular findings.
RESULTS
Whole exome sequencing was performed on fetal DNA and parental blood. Two fetal heterozygous novel variants of , c.2304_2307delTCAA (p.Asn768Lysfs*7) and c.2128_2129delAT (p.lle710Cysfs*19), were inherited from the mother and father, respectively. Both variants created a reading frameshift leading to a premature stop codon and loss of protein function.
CONCLUSION
To our knowledge, this is the first Latin American report with clinical, radiographic, and molecular diagnosis of ACG1A. Clinical and molecular diagnosis in utero is essential for genotype-phenotype correlation and is useful for providing better genetic counseling.
PubMed: 29872333
DOI: 10.2147/TACG.S157235 -
Pediatric Research Sep 1987Immune and lectin histochemical and microchemical methods were employed to study growth cartilage from seven cases of achondrogenesis type II (Langer-Saldino). The...
Immune and lectin histochemical and microchemical methods were employed to study growth cartilage from seven cases of achondrogenesis type II (Langer-Saldino). The normal architecture of the epiphyseal and growth plate cartilage was replaced by a morphologically heterogeneous tissue. Some areas were comprised of vascular canals surrounded by extensive fibrous tissue and enlarged cells that had the appearance and histochemical characteristics of hypertrophic chondrocytes. Other areas contained a mixture of cells ranging from small to the enlarged chondrocytes. The extracellular matrix in the latter areas was more abundant and had characteristics of both precartilage mesenchymal matrix and typical cartilage matrix; it contained types I and II collagen, cartilage proteoglycan, fibronectin, and peanut agglutinin binding glycoconjugate(s). Peptide mapping of cyanogen bromide cartilage collagen peptides revealed the presence of types I and II collagen. These observations could be explained by a defect in the biosynthesis of type II collagen or in chondrocyte differentiation.
Topics: Bone Diseases, Developmental; Collagen; Extracellular Matrix; Growth Plate; Humans; Hypertrophy; Immunoenzyme Techniques; Infant, Newborn
PubMed: 3309860
DOI: 10.1203/00006450-198709000-00017 -
Archives of Disease in Childhood Jul 1976The clinical, pathological, and radiological features of 2 male sibs with a severe and lethal form of micromelic dwarfism are desribed. The family also includes 2 normal...
The clinical, pathological, and radiological features of 2 male sibs with a severe and lethal form of micromelic dwarfism are desribed. The family also includes 2 normal sibs. The histological and radiological appearances suggested a diagnosis of achondrogenesis type I, but the markedly deficient ossification of the skull and the presence of intrauterine rib fractures were atypical. These changes have been observed in two other families with 2 or more infants with suspected achondrogenesis, raising the possibility that these familial cases may be a subvariant of achondrogesis or even a distinct disease entity. The disease appears to be inherited as an autosomal recessive and death occurs shortly after birth because of severe pulmonary hypoplasia.
Topics: Achondroplasia; Bone and Bones; Dwarfism; Female; Humans; Infant, Newborn; Lung; Male; Osteogenesis; Pregnancy; Radiography
PubMed: 962365
DOI: 10.1136/adc.51.7.550 -
Australasian Radiology Jun 1976
Topics: Dwarfism; Ectromelia; Humans; Infant, Newborn; Male; Radiography
PubMed: 1021128
DOI: 10.1111/j.1440-1673.1976.tb02014.x -
Pediatric Radiology 1986A new type of neonatal death dwarfism, resembling the achondrogenesis syndromes on clinical examination but presenting distinctive radiographic and microscopic features...
A new type of neonatal death dwarfism, resembling the achondrogenesis syndromes on clinical examination but presenting distinctive radiographic and microscopic features has been described. It presents another, new form of achondrogenesis.
Topics: Achondroplasia; Growth Plate; Humans; Infant, Newborn; Male; Syndrome; Thanatophoric Dysplasia
PubMed: 3748652
DOI: 10.1007/BF02386829 -
The Journal of Pediatrics Apr 1973
Topics: Achondroplasia; Bone and Bones; Cartilage Diseases; Cleft Palate; Diagnosis, Differential; Dwarfism; Eye Abnormalities; Female; Humans; Infant, Newborn; Karyotyping; Limb Deformities, Congenital; Nose; Ossification, Heterotopic; Radiography
PubMed: 4633363
DOI: 10.1016/s0022-3476(73)80592-x -
Pediatric and Developmental Pathology :... 2007Achondrogenesis type IA (Houston-Harris) is an extremely rare lethal chondrodysplasia with a characteristic severe disarrangement of endochondral ossification. The...
Achondrogenesis type IA (Houston-Harris) is an extremely rare lethal chondrodysplasia with a characteristic severe disarrangement of endochondral ossification. The growth plate cartilage completely lacks columnar-zone formation and shows chondrocyte expansion due to intracellular vacuoles. This article on a new case of achondrogenesis type IA confirms these findings and demonstrates, on the ultrastructural level, the retention of fine fibrillar material within the rough endoplasmic reticulum (rER). Molecular analysis in the presented case of achondrogenesis type IA did not reveal mutations in the COL2A1 and SLC26A2 genes, which are known to cause achondrogenesis types IB and type II. Although the extracellular cartilage matrix was severely altered, all of the investigated matrix molecules (collagens, aggrecan, matrilins, cartilage oligomeric protein [COMP]) showed a normal distribution pattern. The only exception was type-X collagen, which was significantly reduced. Overall, our study suggests a disturbance in cartilage matrix assembly in the present case due to the retention of some sort of matrix component within the rER. Presumably, as a consequence of this event, processes of chondrocyte maturation and differentiation and endochondral bone formation are severely affected in this case of achondrogenesis type IA.
Topics: Abortion, Eugenic; Adult; Anion Transport Proteins; Chondrocytes; Collagen Type II; Collagen Type X; DNA Mutational Analysis; Enchondromatosis; Endoplasmic Reticulum, Rough; Extracellular Matrix Proteins; Female; Fluorescent Antibody Technique, Indirect; Gestational Age; Growth Plate; Humans; Membrane Transport Proteins; Osteochondrodysplasias; Phenotype; Pregnancy; Sulfate Transporters
PubMed: 17638425
DOI: 10.2350/06-07-0134.1 -
Ryoikibetsu Shokogun Shirizu 2001