Non-Mendelian Inheritance - Lesson 1: Triplet Repeat Disorders


Myotonic dystrophy pedigree with increasing severity and decreasing age of onset.
Myotonic dystrophy pedigree with increasing severity and decreasing age of onset.

1.1   Triplet Repeat Expansion



Repeat Ranges for Huntington  Disease
Repeat Ranges for Huntington  Disease

1.2   Expansion of Triplet Repeats



Individuals with fragile X syndrome (left) and a family with myotonic dystrophy
Individuals with fragile X syndrome (left) and a family with myotonic dystrophy
(L: Reprinted from J Pediatr, 96(5), Turner G, Daniel A, Frost M, "X-linked mental retardation, macro-orchidism, and the Xq27 fragile site", 837, 1980, with permission from Elsevier Science; R: Reprinted from Medical Genetics, 2nd ed., Jorde LB, et al, 2000, with permission from Elsevier Science.)

1.3   Triplet Repeat Disorders



Boys with fragile X syndrome
(Reprinted from Medical Genetics, 2nd ed., Jorde LB, et al, 2000, with permission from Elsevier Science.)

1.3.1   Fragile X Syndrome

Description

CGG repeat size

Normal range

6 to 40

Intermediate range

41 to 60

Premutation range

61 to 200

Affected range

Greater than 200



Notice the variable severity and presentation in the facies of  this three generation family with myotonic dystrophy. The infant has more than 1000 repeats, whereas the mother and grandmother each have about 100 repeats
(Reprinted from Medical Genetics, 2nd ed., Jorde LB, et al, 2000, with permission from Elsevier Science.)

1.3.2   Myotonic Dystrophy
(or dystrophia myotonica or DM)

Description

CTG repeat size

Normal range

5 to 37

Premutation range
(No symptoms, but children at risk)

38 to 49

Mild

50 to about 150

Classical

About 100 to 1000-1500

Congenital

About 1000 and greater



1.3.3   Huntington Disease

Description

CAG repeat size

Normal range

10 to 26

Premutation range

27 to 41

Affected range

36 to 121