Laminopathy

Normal nuclear lamina (a and b) and mutant nuclear lamina (c and d) from a patient with HGPS

Laminopathies are a subset of genetic disorders that arise from mutations in genes responsible for encoding proteins of the nuclear lamina. Part of a broader category termed nuclear envelopathies, these diseases relate to defects in the nuclear envelope. Ever since the identification of laminopathies in the late 1990s, extensive research has begun to shed light on the critical role nuclear envelope proteins play in maintaining cellular and tissue integrity in animals.

Symptoms

Laminopathies, together with other nuclear envelopathies, manifest in a wide range of clinical symptoms. Notable among these are:

• Skeletal and cardiac muscular dystrophies
• Lipodystrophy and diabetes
• Dermal and neuropathic conditions
• Dysplasia
• Leukodystrophy
• Progeria (premature aging)

While most symptoms tend to emerge postnatally, specifically during childhood or adolescence, certain laminopathies might result in premature mortality. For instance, mutations within the lamin B (LMNB1 gene) can prove lethal either at or before birth.

Genetics

Fundamentally, individuals diagnosed with a classic laminopathy exhibit mutations in the LMNA gene, which encodes for lamin A/C. Later discoveries have linked mutations in the lamin B (LMNB2 gene) and genetic defects that alter lamin B abundance to laminopathies. Other implicated genes in nuclear envelopathies encode for lamin-binding proteins such as:

• Lamin B receptor (LBR gene)
• Emerin (EMD gene)
• LEM domain-containing protein 3 (LEMD3 gene)
• Prelamin-processing enzymes like the zinc metalloproteinase STE24 (ZMPSTE24 gene)

Laminopathies can stem from both recessive and dominant alleles, with rare instances of de novo mutations generating dominant alleles that may prevent carriers from reproducing before they perish. The most prevalent nuclear envelopathy in humans is the Emery-Dreifuss muscular dystrophy, which is traced back to an X-linked mutation in the EMD gene encoding for emerin. This condition affects approximately 1 in 100,000 individuals.

External links

• GeneReview/NIH/UW entry on LMNA-Related Dilated Cardiomyopathy

Laminopathy Resources
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