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We report a patient with developmental delay, brachydactyly type E, short stature, and tetralogy of Fallot. Brachydactyly-mental retardation syndrome (BDMR) was suspected based on the phenotype; however, array CGH excluded a 2q37 deletion, but identified a deletion encompassing the SHOX gene. BDMR is characterized by cognitive impairment, skeletal abnormalities involving hands and feet, short stature, and overweight. Most affected individuals carry relatively large 2q37 deletions encompassing HDAC4. This gene encodes a histone deacetylase involved in epigenetic regulation of cell growth and differentiation, specifically during endochondral bone formation in chondrocyte hypertrophy. Since SHOX haploinsufficiency can cause skeletal defects and short stature but would not fully explain the clinical picture of this patient, exome sequencing was performed, and a heterozygous HDAC8 frameshift mutation was identified. HDAC8 is a distinct histone deacetylase involved in cohesin recycling and is responsible for an X-linked dominant Cornelia de Lange-like phenotype. A new blended clinical phenotype may be explained by the result of a dual molecular diagnosis, which represents a combination of 2 independent genetic defects, with relevant implications for genetic counseling, clinical management, and prognosis.
This article was published in the following journal.
Name: Cytogenetic and genome research
Background The short stature homeobox-containing (SHOX) gene strongly affects height. Therefore, a better understanding of SHOX haploinsufficiency could be advantageous to early diagnosis and treatmen...
Eighteen histone deacetylases exist in mammals. The class 1 histone deacetylases HDAC1 and HDAC2 are important for oogenesis and fertility in mice, likely via their effects on histones. The reproducti...
Deletions on chromosome 15q14 are a known chromosomal cause of cleft palate, typically co-occurring with intellectual disability, facial dysmorphism, and congenital heart defects. The identification o...
Turner syndrome was first described to encompass a shared set of physical features displayed by a subset of female patients including short stature and lack of sexual development. Half of cases are du...
Enzymes from the histone deacetylase (HDAC) family are highly regulated by different mechanisms. However, only very limited knowledge exists about the regulation of HDAC8, an established target in mul...
GeNeSIS is an open-label, multinational, multicenter, observational study to evaluate the safety and effectiveness of Humatrope treatment. GeNeSIS is a modular program that includes: ...
This clinical trial will compare the mean first year height velocity of somatropin-treated prepubertal patients with SHOX deficiency with the height velocity of a control group of untreate...
The celiac disease (CD) is a disease with an immune and genetic component that is activated by the presence of gluten, and damages the intestine mucosa and causes malabsorption of food. ...
Each year in the United States, thousands of babies are born with heart defects. Women who take folic acid during pregnancy have a lower risk of giving birth to infants with heart defects,...
To identify genes involved in the pathogenesis of three types of congenital heart disease, atrial septal defects, paramembranous ventricular septal defects, and atrioventricular canal defe...
A copy number variation that results in reduced GENE DOSAGE due to any loss-of-function mutation. The loss of heterozygosity is associated with abnormal phenotypes or diseased states because the remaining gene is insufficient.
A growth differentiation factor that plays a role in the genesis of left-right asymmetry during vertebrate development. Evidence for this role is seen in MICE where loss of growth differentiation factor 1 function results in right-left isomerism of visceral organs. In HUMANS heterozygous loss of growth differentiation factor 1 function has been associated with CONGENITAL HEART DEFECTS and TRANSPOSITION OF GREAT VESSELS.
Loss or absence of normal intestinal function due to nerve damage or birth defects. It is characterized by the inability to control the elimination of stool from the body.
A genetically heterogeneous disorder caused by hypothalamic GNRH deficiency and OLFACTORY NERVE defects. It is characterized by congenital HYPOGONADOTROPIC HYPOGONADISM and ANOSMIA, possibly with additional midline defects. It can be transmitted as an X-linked (GENETIC DISEASES, X-LINKED), an autosomal dominant, or an autosomal recessive trait.
An autosomal dominant disorder manifested by various combinations of preauricular pits, branchial fistulae or cysts, lacrimal duct stenosis, hearing loss, structural defects of the outer, middle, or inner ear, and renal dysplasia. Associated defects include asthenic habitus, long narrow facies, constricted palate, deep overbite, and myopia. Hearing loss may be due to Mondini type cochlear defect and stapes fixation. (Jablonski's Dictionary of Syndromes & Eponymic Diseases, 2d ed)
A diagnostic test is any kind of medical test performed to aid in the diagnosis or detection of disease. For example: to diagnose diseases to measure the progress or recovery from disease to confirm that a person is free from disease Clin...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...