The Invitae Rhizomelic Chondrodysplasia Punctata Spectrum Panel analyzes, three genes that are associated with rhizomelic chondrodysplasia punctata (RCDP), a spectrum of peroxisome biogenesis disorders. This test is indicated for any individual in whom RCDP is suspected based on clinical or laboratory findings. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of disease-causing variants provide accurate risk assessment and determine carrier status in at-risk relatives.
AGPS GNPAT PEX7
AGPS GNPAT PEX7
Rhizomelic chondrodysplasia punctata (RCDP) is a spectrum of disorders of peroxisome biogenesis which are characterized by rhizomelic shortening of the upper extremities, contractures, bilateral congenital cataracts, dysmorphic facial features, seizures and severe growth and developmental delay. Punctate epiphyseal calcifications, metaphyseal dysplasia and vertebral coronal clefts are seen on skeletal X-rays. Brain anomalies have been reported on cranial MRI (white matter abnormalities, cerebral and cerebellar atrophy). Life expectancy is usually shortened and affected children may only survive the first decade. However, a milder phenotype has been reported in some patients that lack rhizomelic shortening and resemble an adult refsum phenotype. This condition can be divided into 3 different types, according to genetic cause: type 1 (PEX7), type 2 (GPNAT) and type 3 (AGPS).
Biochemical findings include of RCDP include decreased red blood cell plasmalogens and normal plasma levels of very long chain fatty acids. In addition, plasma levels of phytanic acid are increased in RCDP type I.
Among individuals with a clinical diagnosis of RCPD, greater than 90% of individuals had pathogenic sequence variants in PEX7. Subtypes caused by pathogenic variants in GPNAT and AGPS are rare.
All types of RCDP are inherited in an autosomal recessive manner.
The prevalence of RCDP type 1 is estimated to be lower than 1:100,000, and type 2 and 3 are more rare than type 1.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|