Invitae Lujan Syndrome Test


Test description

The Invitae Lujan Syndrome Test analyzes the gene MED12, which is known to be associated with Lujan syndrome (LS) and other MED12-spectrum disorders. Previously, traditional testing strategies for MED12-related disorders included initial testing of exons 21 and 22 of the MED12 gene to evaluate for p.Asn1007Ser (the recurring pathogenic variant for LS) and for other MED12 reported variants; when this initial testing was negative, sequence analysis of the remaining exons would have been considered. The Invitae Lujan Syndrome test analyzes the full coding region of the MED12 gene and eliminates the need for the former tiered-test approach.

Because LS shares clinical findings with other MED12-spectrum disorders, the diagnosis of LS relies on molecular genetic testing. Additionally, clinical findings associated with MED12 spectrum disorders are nonspecific, which may lead to clinical overdiagnosis. Identifying a genetic change related to Lujan syndrome can guide medical management, including early individualized education plans, early intervention for physical, occupational and speech therapy for developmental delays, and management of other clinical findings.

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Primary panel (1 gene)


Lujan syndrome

Lujan syndrome (LS) is a multisystemic developmental disorder and is one of the two most well-defined disorders within the spectrum of MED12-related disorders. MED12-related disorders are generally characterized by hypotonia, abnormalities of the corpus callosum, intellectual disability, and behavioral problems. Individuals with Lujan syndrome may also present with physical abnormalities such as macrocephaly, distinctive facial features, and Marfan-like features. Marfan-like features include a tall, thin body, long limbs and fingers, and joint hypermobility. Additional clinical findings may include abnormal speech, heart defects, seizures, and abnormalities of the urogenital system. The clinical presentation is variable; not all individuals with Lujan syndrome will present with every characteristic described above.

The clinical sensitivity for this test has not yet been determined.

LS is inherited in an X-linked pattern.

The penetrance of this disorder is presumed to be 100% in males. To date, the published variants in MED12 (p.Arg961Trp, p.Gly958Glu, and p.Asn1007Ser) have not been observed in unaffected males. The clinical presentation is variable. Female carriers for LS are typically unaffected.

The prevalence for Lujan syndrome is unknown.

The presence of six of the following eight clinical findings is suggestive of a clinical diagnosis of Lujan syndrome: intellectual disability; low muscle tone; macrocephaly; tall, thin body; long, thin face; prominent nasal bridge; high, narrow palate; and short philtrum.

Assay and technical information

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
MED12 NM_005120.2