Mutation Types in DMD

Mutation type	Frequency
Exon deletions	~60–70% (most common)
Exon duplications	~5–10%
Point mutations (nonsense, frameshift, splice)	~20–30%
Small indels	Small percentage

In De Novo DMD

• About 1/3 of DMD cases are de novo

Among de novo mutations:

Mutation	Relative frequency
Deletions	Most common
Point mutations	Next most common
Duplications	Less common

Deletions Are So Common in DMD

The DMD gene is:

• The largest gene in the human genome
• Located on Xp21
• Contains 79 exons
• Extremely mutation-prone

Deletion hotspots:

• Exons 45–55 (most common)
• Exons 2–20 (secondary hotspot)

• Unequal recombination → deletions

Carrier Status Distribution

Status	Frequency
Carrier mother	~2/3
De novo mutation	~1/3

Germline Mosaicism Risk

If mother tests negative:

Recurrence risk is still: ~4–15%

Due to: Germline mosaicism

DMD Be Suspected Prenatally Without Family History?

Typical DMD:

• Normal fetal anatomy
• Normal movements
• No structural abnormalities

Prenatal suspicion without family history is difficult.

Rare Prenatal Clues

• Reduced fetal movements (late)
• Mild polyhydramnios
• Muscle hypotonia features

But: These are nonspecific and unreliable.

Genetic Testing Strategy

The DMD gene has:

• Large size (79 exons)
• High deletion/duplication rate
• Significant proportion of point mutations

MLPA + NGS together give full coverage.

MLPA (Multiplex Ligation-dependent Probe Amplification)

Best for:

• Exon deletions
• Exon duplications

Detection rate: ~70–75% of DMD mutations

Limitation:

• Cannot detect:
• Point mutations
• Small insertions/deletions
• Splice variants

NGS (Next Generation Sequencing)

Best for:

• Point mutations
• Small indels
• Splice-site variants
• Nonsense mutations

Detection rate: ~20–30%

Strength:

Detects mutations MLPA misses.

Prenatal Diagnosis Without Known Mutation

Both MLPA and NGS should be used.

MLPA → then NGS; Sequential approach.