Disease relevance of Dwarfism

• Achondroplasia, the most common genetic form of dwarfism, is caused by mutations in FGFR3 [1].
• MT1-MMP deficiency causes craniofacial dysmorphism, arthritis, osteopenia, dwarfism, and fibrosis of soft tissues due to ablation of a collagenolytic activity that is essential for modeling of skeletal and extraskeletal connective tissues [2].
• Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism [3].
• Single allele-inactivating mutations in the promoter of human NPR-A are associated with hypertension and heart failure, whereas homozygous inactivating mutations in human NPR-B cause a form of short-limbed dwarfism known as acromesomelic dysplasia type Maroteaux [4].
• This virus, designated RA-1, elicits a syndrome in neonatal mice that includes neurological disturbances, permanent crippling of limbs, dwarfism, alopecia, blepharitis, "masking," and a rigid curvature of the thoracic spine [5].

Psychiatry related information on Dwarfism

• The Dyggve-Melchior-Clausen syndrome is an inherited disorder of skeletal development characterized by short-trunked dwarfism, mental retardation, and a distinctive pattern of bone changes [6].
• A MELAS patient with dwarfism and impaired adolescent development had decreased growth hormone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) [7].

High impact information on Dwarfism

• The mutation confers a phenotype including marked microcephaly (head circumference 12 s.d. below the mean) and dwarfism (5 s.d. below the mean) [8].
• Here, we report large-scale deletions (in seven families) and a nonsense mutation (in one family) of SHOX in patients with DCS and show that Langer mesomelic dwarfism results from homozygous mutations at the DCS locus [9].
• Heterozygous mutations in SOX9 lead to a human dwarfism syndrome, Campomelic dysplasia [10].
• TD, characterized by neonatal lethality and profound dwarfism, is the result of FGFR3 mutations, including an R248C substitution in the extracellular domain or a K650E substitution in the tyrosine kinase (TK) domain [11].
• The cpd mutant displays de-etiolation and derepression of light-induced genes in the dark, as well as dwarfism, male sterility, and activation of stress-regulated genes in the light [12].

Chemical compound and disease context of Dwarfism

• Anterior pituitary hypoplasia and dwarfism in mice lacking the dopamine transporter [13].
• Deletion of the dopamine transporter (DAT) results in increased dopaminergic tone, anterior pituitary hypoplasia, dwarfism, and an inability to lactate [13].
• The disease-resistant Arabidopsis thaliana aberrant growth and death2 (agd2-1) mutant has elevated levels of the defense signal salicylic acid (SA), altered leaf morphology, and mild dwarfism [14].
• Oral supplementation of BH(4) and neurotransmitter precursors completely rescued dwarfism and phenylalanine metabolism [15].
• Two male patients, aged 6 and 25, both with normal intelligence and absence of neurological abnormalities, exhibited dysostosis multiplex, dwarfism, odontoid anomalies, cloudy corneas, exessive excretion of keratan sulfate, and abnormal urinary oligosaccharides [16].

Biological context of Dwarfism

• A human dwarfism mutation that affects positive control in the related POU domain protein Pit-1 maps to the same region of the HTH motif as do positive control mutations in lambda repressor [17].
• Missense mutations in fibroblast growth factor receptor 3 (FGFR3) result in several human skeletal dysplasias, including the most common form of dwarfism, achondroplasia [18].
• This is the first dominant dwarf rat strain to be reported and will provide a valuable model for evaluating the effects of transgene expression on endogenous GH secretion, as well as the use of GH secretagogues for the treatment of dwarfism [19].
• Given the sequence homology between the extracellular domain of the GHR and a soluble GH-binding protein (GH-BP), it is remarkable that GH-BP binding activity is absent from the serum of patients with Laron-type GH insensitivity, a hereditary form of severe dwarfism [20].
• A point mutation, Gly380Arg, in the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) leads to achondroplasia, the most common form of genetic dwarfism in humans [21].

Anatomical context of Dwarfism

• Here we show that targeted overexpression of CNP in chondrocytes counteracts dwarfism in a mouse model of achondroplasia with activated fibroblast growth factor receptor 3 (FGFR-3) in the cartilage [22].
• The cGKII-deficient mice also developed dwarfism that was caused by a severe defect in endochondral ossification at the growth plates [23].
• Genetic disruption of SRC-3 in mice results in a pleiotropic phenotype showing dwarfism, delayed puberty, reduced female reproductive function, and blunted mammary gland development [24].
• periostin null mice exhibit dwarfism, incisor enamel defects, and an early-onset periodontal disease-like phenotype [25].
• Mutations that cause constitutive activation of fibroblast growth factor receptor 3 (FGFR3) result in skeletal disorders that are characterized by short-limbed dwarfism and premature closure of cranial sutures [26].

Gene context of Dwarfism

• Smad6/Smurf1 overexpression in cartilage delays chondrocyte hypertrophy and causes dwarfism with osteopenia [27].
• Dwarfism could be rescued by the application of brassinolide, suggesting that DWF4 plays a role in brassinosteroid (BR) biosynthesis [28].
• The Nppc(-/-) mice show severe dwarfism as a result of impaired endochondral ossification [29].
• Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects [30].
• Hip1-related mutant mice grow and develop normally but have accelerated spinal abnormalities and dwarfism in the absence of HIP1 [31].

Analytical, diagnostic and therapeutic context of Dwarfism

• Loss of the entire ERECTA family genes led to striking dwarfism, reduced lateral organ size and abnormal flower development, including defects in petal polar expansion, carpel elongation, and anther and ovule differentiation [32].
• The hepatic radioreceptor assay for hGH has been applied to the detection of hGH in the sera of patients with high growth hormone dwarfism (Laron dwarfism) [33].
• These rats show reduced pituitary size, GH deficiency, and dominant dwarfism, but are large enough for serial blood sampling studies to examine their spontaneous GH secretion and responses to GRF, somatostatin, and GH-releasing peptide-6 (GHRP-6) [34].
• Ketamine induction for cesarean section in a patient with acute intermittent porphyria and achondroplastic dwarfism [35].
• The main features are intrauterine growth failure with very low birthweight; disproportionate dwarfism with predominantly distal shortening of limbs; small cubitally inclined clenched hands; microcephaly with Seckel-like facies and delayed psychomotor development [36].

References