Which genetic abnormality underlies DiGeorge syndrome as described?

Which genetic abnormality underlies DiGeorge syndrome as described?

• A. Trisomy of chromosome 21
• B. Deletion of a portion of chromosome 22
• C. Duplication of chromosome 18
• D. Mutation in a single nucleotide in chromosome 22

Answer: (B)

A missing segment of chromosome 22 underlies DiGeorge syndrome. Specifically, a microdeletion at 22q11.2 reduces the dosage of several genes, most notably TBX1, which disrupts the development of the third and fourth pharyngeal pouches. This leads to thymic hypoplasia (immune deficiency), absent or underdeveloped parathyroids (hypocalcemia), and characteristic heart and facial anomalies. This is a deletion, not a whole extra chromosome or a single base change, which is why other options like trisomy of chromosome 21, duplication of chromosome 18, or a point mutation on chromosome 22 do not describe the underlying cause. Detecting this deletion is typically done with methods like FISH or microarray, since it is a microdeletion that may not be visible on a standard karyotype.

A missing segment of chromosome 22 underlies DiGeorge syndrome. Specifically, a microdeletion at 22q11.2 reduces the dosage of several genes, most notably TBX1, which disrupts the development of the third and fourth pharyngeal pouches. This leads to thymic hypoplasia (immune deficiency), absent or underdeveloped parathyroids (hypocalcemia), and characteristic heart and facial anomalies. This is a deletion, not a whole extra chromosome or a single base change, which is why other options like trisomy of chromosome 21, duplication of chromosome 18, or a point mutation on chromosome 22 do not describe the underlying cause. Detecting this deletion is typically done with methods like FISH or microarray, since it is a microdeletion that may not be visible on a standard karyotype.