Genetic Disorders Info

t(1;19)(q21 or 23;p13)
The t(1;19) or the der(19) from the t(1;19) rearrangement is almost exclusively observed in pre-B cell acute lymphocytic leukemia (ALL) with FAB-L1 morphology.  The t(1;19) ALL does not usually show extreme leukocytosis and suggests a relatively poor patient prognosis ...

t(8;21)(q22;q22)
The t(8;21) rearrangement is almost exclusively observed in acute nonlymphocytic leukemia (ANLL) and specifically in acute myloid leukemia (AML:FAB M2).  The t(8;21) is also associated with a large number of cells showing auer rods.  Additional chromosome changes are observed in over 75 percent of t(8;21) cases which also include the loss of a sex chromosome, a deleted 9q, trisomy 8, and monosomy 7.  The presence of the t(8;21) alone has been reported to indicate a relatively good patient  prognosis.

Inv(16)(p13q22)
Inversions of chromosome 16 and rearrangements involving band 16q22 are almost exclusively observed in acute nonlymphocytic leukemia, specifically acute myelomonocytic leukemia (AMMoL:FAB-M4eo). This chromosome abnormality is associated with increased numbers of immature eosinophils in the bone marrow and peripheral blood. Eosinophils may show some nuclear hypo-segmentation and positive PAS/PE staining. These patients have been reported to frequently develop CNS leukemia. The inversion of chromosome 16 or a band 16q22 abnormality is reported to be suggestive of a relatively good patient prognosis.

Inv(3)(q21q26),dup(3q),t(3q;3q)
Rearrangements of the chromosome 3 long arm, particularly in the q21/q26 band region, have been observed in acute nonlymphocytic leukemia (ANLL), chronic myelocytic leukemia(CML) and myelodysplastic syndromes. Thrombocytosis and abnormal megakaryocytopoiesis with the presence of micromegakaryocytes and hypolobulated nuclei are most often observed ...

t(15;17)(q22;q21 or12)
This translocation is a remarkably specific marker for acute promyelocytic leukemia (ANLL-M3).  This strong association is further exemplified by the fact that occasionally this translocation develops as a secondary aberration during CML blast transformation, with patients exhibiting disease characteristics indistinguishable from APL. Apart from these exceptional CML blast crisis patients, t(15;17) has not been detected in any malignancies other than ANLL-M3.  t(15;17) APL patients usually exhibit disseminated intravascular coagulation (DIC) and hyper- or micro-granulated promyelocytes.

Angelman syndrome results from absence of a functional copy of the UBE3A gene inherited from the mother.

+12
Trisomy of chromosome 12 is most frequently observed in B-cell chronic lymphocytic leukemia(CLL).  It has also been observed in other types of neoplasms.  As a single chromosome change, +12-CLL patients have been reported to have a relatively good prognosis, while +12-CLL patients with additional chromosome changes may suggest a relatively poor prognosis.

The gene responsible in this disorder, blm, was mapped to 15q26.1 and its product was found to encode a RecQ DNA helicase.  It is involved in DNA replication and repair.  Bloom syndrome is an autosomal recessive disorder.  The predominant mutation is referred to as “blmAsh”, a 6-bp deletion and 7-bp insertion at nucleotide position 2281.

Canavan disease is caused by a defective aspa gene.  This gene is located on the p arm of chromosome 17, and is responsible for the production of the enzyme aspartoacylase.  This deficiency leads to the buildup of N-acetylaspartic acid (NAA) in the brain.  The accumulated NAA causes a chemical imbalance resulting in myelin destruction.  Canavan disease is an autosomal recessive disorder.

t(9;22)(q34;q11 or 12) Philadelphia Chromosome
The translocation between chromosome 9 and 22 yielding the Philadelphia chromosome (Ph1) is most consistent with chronic myelogenous (granulocytic) leukemia (CML), although it has also been observed in acute lymphocytic leukemia (ALL). In CML, the Ph1 is reported to indicate a relatively good prognosis, while in ALL it is associated with a relatively poor prognosis. The presence of chromosome changes in addition to the Ph1, e.g. +8, iso(17q),+9, +Ph1, is a indication of a blastic phase of CML and poor patient prognosis.

CF is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, found at the q31.2 locus of chromosome 7.  The CFTR gene produces a chloride ion channel important in creating sweat, digestive juices, and the mucus glands of the lungs, liver, pancreas, and intestines.  CF develops when neither allele can produce a functional CFTR protein.  CF is an autosomal recessive disease.

DiGeorge syndrome is caused by a deletion on chromosome 22.  Approximately 90% of patients with DiGeorge syndrome have a deletion at the 22q11.2 region.  A small number of cases of DGS have defects on other chromosomes, notably 10p13. DiGeorge syndrome is inherited in an autosomal dominant manner.