Structural Aberrations and Microdeletion Syndromes

Flashcards covering structural chromosome aberrations, including deletions, inversions, translocations, and related microdeletion syndromes.

Structural Aberrations

Abnormality of structure and genetic content due to chromosome break and loss or union of broken ends.

Stable Mutant Chromosome

Characterized by having 1 centromere and 2 telomeres (pter, qter).

Unstable Mutant Chromosome

Examples include dicentric and ring chromosomes.

Chromosomal Mutation Timing

Occurs pre-S phase.

Chromatidic Mutation Timing

Occurs post-S phase; isochromatidic resembles chromosomal due to two mutational events.

Balanced Structural Aberration

Rearrangement of chromosomal regions with no gain or loss of genetic material; often normal phenotype (ins, inv, rcp).

Unbalanced Structural Aberration

Gain or loss of genetic material leading to abnormal phenotype (deletion, i, r, dic).

Deletion (del)

Unbalanced structural aberration involving loss of a chromosomal fragment, resulting in partial monosomy.

Terminal Deletion

One chromosome, one breaking point, resulting in loss of a terminal fragment.

Interstitial Deletion

One chromosome, two breaking points, resulting in loss of interstitial fragment and reattachment of remaining fragments.

Microscopic Deletions

Can be studied using light microscopy and classical cytogenetic techniques; examples include Wolf Hirschhorn and Cri du chat syndromes.

Submicroscopic Deletion/Microdeletion

Studied using molecular cytogenetic techniques (FISH); associated with contiguous gene syndromes like Prader-Willi, Angelman, Williams, and DiGeorge.

Ring Chromosome (r)

One chromosome with two breaking points on different arms leading to loss of terminal fragments and reattachment of remaining ends; high instability.

Inversion (inv)

One chromosome with two breaking points; balanced rearrangement with no loss or gain of genetic material.

Pericentric Inversion

Two breaking points on different arms; middle fragment containing centromere rotates 180° and reattaches, changing chromosome morphology.

Paracentric Inversion

Two breaking points on the same arm; rotating fragment does not contain centromere, morphology stays unchanged.

Isochromosome (i)

Perfect metacentric chromosomes made of two identical arms, caused by abnormal mitotic cell division.

Duplication (dup)

Involves two homologous chromosomes; unbalanced mutation leading to partial trisomy of the duplicated fragment.

Insertion (ins)

Involves two non-homologous chromosomes; transfer of chromosomal fragment from one chromosome to a non-homologous chromosome.

Reciprocal Translocation (rcp)

Involves two non-homologous chromosomes; balanced, mutual exchange of acentric fragments with no gain or loss of genetic material.

Robertsonian Translocation (rob)

Involves two acrocentric chromosomes; long arms fuse at centromere, short arms often lost, total chromosome number is 45.

Dicentric Chromosomes (dic)

Involves two chromosomes; unbalanced mutation resulting in loss of telomeres, reattachment of centric fragments, and total chromosome number of 45.

Cri du Chat Syndrome

Caused by terminal deletion on the short arm of chromosome 5; characterized by distinct cat-like cry and various physical and mental impairments.

Wolf-Hirschhorn Syndrome

Partial monosomy of chromosome 4 (deletion of 4p-); presents with growth retardation, craniofacial dysmorphism, and severe mental retardation.

Prader-Willi Syndrome

Caused by paternal deletion of 15q11-13 or maternal uniparental disomy; features include muscular hypotonia, feeding difficulties, and later, bulimia and obesity.

Angelman Syndrome

Caused by maternal deletion of 15q11-13 or paternal uniparental disomy; characterized by severe mental retardation, jerky movements, absence of speech, and uncontrollable laughter.

Williams Syndrome

Microdeletion on the long arm of chromosome 7 (del(7)(q11.23)); associated with facial dysmorphism, aortic stenosis, and mental retardation.

DiGeorge/Velo-Cardio-Facial Syndrome (VCFS)

Caused by microdeletion of 22q11.2 or deletion of 10p13; characterized by cardiac anomalies, abnormal face, thymic hypoplasia, cleft palate, and hypocalcemia (CATCH 22).