The Invitae Renpenning Syndrome Test analyzes the PQBP1 gene that is associated with Renpenning syndrome. Renpenning syndrome is characterized by intellectual disability, microcephaly, short stature, and dysmorphic facial features.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.
Renpenning syndrome is a rare variable condition characterized by intellectual disability, microcephaly, short stature and dysmorphic facial features including a long triangular face, upslanting or downslanting palpebral fissures, long prominent nose, large or dysplastic protruding ears, sparse eyebrows and hair. Other reported features include failure to thrive, growth restriction, extrapyramidal features, spasticity, seizures and muscular atrophy. Major malformations occur occasionally, including cardiac defects, cleft palate, and genital and anal anomalies.
PQBP1 is the only gene known to be associated with Renpenning syndrome. All of the individuals reported to date have been found to have a pathogenic variant in PQBP1. The percentage of individuals with X-linked intellectual disability who have a pathogenic change in PQBP1 has not been well-established.
Renpenning syndrome is inherited in an X-linked recessive manner.
Renpenning syndrome is highly penetrant with clinical variability. Carrier females are generally unaffected, although they may exhibit very mild symptoms.
The prevalence of Renpenning syndrome is not clearly established.
This test may be considered for individuals who exhibit the following features:
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|