Ehlers-Danlos Syndrome Kyphoscoliotic Form, Type VI (PLOD1) Sequencing and Deletion/Duplication

Background Information for Ehlers-Danlos Syndrome Kyphoscoliotic Form, Type VI (PLOD1) Sequencing and Deletion/Duplication:
Characteristics of Ehlers-Danlos Syndrome Kyphoscoliotic Form, Type VI: Kyphoscoliosis at birth or within the first year of life, severe neonatal hypotonia, thin hyperextensible and bruisable skin, atrophic scarring, joint hypermobility, and scleral fragility leading to increased risk for rupture of the globe. Increased risk for rupture of medium size arteries, and individuals with severe kyphoscoliosis are at increased risk for respiratory compromise.
Incidence: Approximately 1 in 100,000 live births.
Inheritance: Autosomal recessive.
Cause: Lysyl hydroxylase deficiency due to pathogenic PLOD1 (procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase) gene mutations.
Clinical Sensitivity: Not published; however, this test combination is expected to detect the majority of mutations.
Methodology: Bidirectional sequencing of the entire coding region and intron/exon boundaries of the PLOD1 gene. Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large PLOD1 coding region deletions/duplications, including the common 8.3kb duplication of exons 10-16.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations and deep intronic mutations will not be detected. Large deletions/duplications of exon 9 will not be detected; large deletions/duplications of exons 1 and 5 may not be detected based on the breakpoints of the rearrangement. The breakpoints of large deletions/duplications will not be determined.