The reference OMIM entry for this protein is 200600

Achondrogenesis, type ia; acg1a
Achondrogenesis, houston-harris type

A number sign (#) is used with this entry because of evidence that achondrogenesis type IA (ACG1A) is caused by homozygous or compound heterozygous mutation in the TRIP11 gene (604505) on chromosome 14q32.

DESCRIPTION

The term achondrogenesis has been used to characterize the most severe forms of chondrodysplasia in humans, invariably lethal before or shortly after birth. Achondrogenesis type I is a severe chondrodystrophy characterized radiographically by deficient ossification in the lumbar vertebrae and absent ossification in the sacral, pubic and ischial bones and clinically by stillbirth or early death (Maroteaux and Lamy, 1968; Langer et al., 1969). In addition to severe micromelia, there is a disproportionately large cranium due to marked edema of soft tissues. - Classification of Achondrogenesis Achondrogenesis was traditionally divided into 2 types: type I (Parenti-Fraccaro) and type II (Langer-Saldino). Borochowitz et al. (1988) suggested that achondrogenesis type I of Parenti-Fraccaro should be classified into 2 distinct disorders: type IA, corresponding to the cases originally published by Houston et al. (1972) and Harris et al. (1972), and type IB (600972), corresponding to the case originally published by Fraccaro (1952). Analysis of the case reported by Parenti (1936) by Borochowitz et al. (1988) suggested the diagnosis of achondrogenesis type II, i.e., the Langer-Saldino type (200610). Type IA would be classified as lethal achondrogenesis, Houston-Harris type; type IB, lethal achondrogenesis, Fraccaro type; and type II, lethal achondrogenesis-hypochondrogenesis, Langer-Saldino type. Superti-Furga (1996) suggested that hypochondrogenesis should be considered separately from achondrogenesis type II because the phenotype can be much milder. - Genetic Heterogeneity of Achondrogenesis Achondrogenesis type IB (ACG1B; 600972) is caused by mutation in the DTDST gene (606718), and achondrogenesis type II (ACG2; 200610) is caused by mutation in the COL2A1 gene (120140).

CLINICAL FEATURES

Houston et al. (1972) described a family from Saskatchewan, Canada, in which 4 of 10 sibs were diagnosed with achondrogenesis. Two were stillborn and 2 died shortly after birth. No osseous tissue or hemopoietic bone marrow was found in the cartilaginous sternum or vertebral bodies. Wiedemann et al. (1974) pointed out the importance of distinguishing achondrogenesis from hypophosphatasia (241500). Smith et al. (1981) reported 3 affected sibs, with in utero diagnosis of the third. Borochowitz et al. (1988) studied the clinical, radiologic, and morphologic features of 17 cases previously diagnosed as achondrogenesis type I. On radiographic analysis, 2 distinct groups of patients were defined based on the presence or absence of rib fractures and ossification of the vertebral pedicles, ischium, and fibula. Microscopic studies of the chondroosseous morphology showed 2 distinct patterns that correlated directly with the radiographic grouping: one group had round, vacuolated chondrocytes with inclusion bodies, ans the other had collagenous rings around the chondrocytes.

MOLECULAR GENETICS

Smits et al. (2010) noted similarities between the skeletal and cellular phenotypes of Trip11 (604505)-null mice and patients with ACG1A, including absence of vertebral-body and skull ossification on radiography, lack of organized columnar zones of proliferating chondrocytes on histologic analysis, reduced expression of COL10A1 (120110) o ... More on the omim web site

Subscribe to this protein entry history

Sept. 22, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 200600 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).