title: Achondrogenesis Type IA (Houston-Harris): a still-unresolved molecular phenotype.
abstract: 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.
authors.affiliation: Institute of Pathology, Liebigstrasse 26, Leipzig, Germany. thomas.aigner@medizin.uni-leipzig.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Aigner
authors.forename: Tilman
authors.initials: T
authors.lastname: Rau
authors.forename: Manuel
authors.initials: M
authors.lastname: Niederhagen
authors.forename: Frank
authors.initials: F
authors.lastname: Zaucke
authors.forename: Markus
authors.initials: M
authors.lastname: Schmitz
authors.forename: Uwe
authors.initials: U
authors.lastname: Pöhls
authors.forename: Helmut
authors.initials: H
authors.lastname: Stöss
authors.forename: Anita
authors.initials: A
authors.lastname: Rauch
authors.forename: Christian T
authors.initials: CT
authors.lastname: Thiel
mesh_terms: D000025:Abortion, Eugenic; D000328:Adult; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism / Q000648:ultrastructure; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D024121:Collagen Type X / Q000378:metabolism; D004252:DNA Mutational Analysis; D004687:Enchondromatosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005865:Gestational Age; D006132:Growth Plate / Q000378:metabolism / Q000473:pathology; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D010009:Osteochondrodysplasias / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D011247:Pregnancy; D000076988:Sulfate Transporters
chemical_list: D027321:Anion Transport Proteins; C499177:COL2A1 protein, human; D024043:Collagen Type II; D024121:Collagen Type X; D016326:Extracellular Matrix Proteins; D026901:Membrane Transport Proteins; C089651:SLC26A2 protein, human; D000076988:Sulfate Transporters