Dysmorphism: Structural anomalies such as widely spaced eyes (hypertelorism) and large head circumference (macrocephaly).
Dysplasia: Abnormal organization of cells in tissue.
Mental retardation: Abnormal intellectual performance, generally determined by an intelligence quotient (IQ) test. Mental retardation is divided into mild (IQ: 50 to 70) or severe (IQ: < 50). Severe mental retardation is subdivided into moderate, severe, and profound.
Methylation: Attachment of methyl groups (–CH3) to cytosine (C) bases. Methylation can regulate the transcription of genes (e.g., reducing the amount of protein generated). Hypermethylation can lead to silencing of a gene and total absence of protein production.
Phenotype: Observed (clinical) findings in a person generated by the interactions between genes and the environment.
Premature ovarian failure: Amenorrhea before the age of 40 years.
Premutation: Trinucleotide repeat expansion within a gene to less than the number of repeats needed for the abnormal phenotype. A premutation can expand to the full mutation and cause the abnormal phenotype in the next generation. For example, most premutation carriers in the fragile X mental retardation 1 (FMR1) gene are phenotypically normal, although women with premature ovarian failure and men with fragile X–associated tremor/ataxia syndrome recently have been described.
Proband: The clinically affected member of a family who comes to medical attention first.
Trinucleotide (or triplet) repeat expansion: Expansion of a segment of DNA within a gene that contains a repeat of three nucleotides (triplet repeats). This increase of triplet repeats happens as the gene is passed on from one generation to another. It can lead to abnormal gene expression and function. Triplet repeat diseases include fragile X syndrome, Huntington disease, myotonic dystrophy, and Friedreich ataxia.
X-linked inherited disorder: Inheritance of a gene that is located on the X chromosome. X-linked recessive inheritance of a disease typically affects males and not females (e.g., hemophilia A). There is no male-to-male transmission (i.e., an affected father will have only unaffected sons). All daughters of an affected father are phenotypically unaffected but are carriers for the gene mutation. On average, one half of sons born to carrier mothers are affected.
