XLID Next-Gen Panel (formerly known as XLMR)

Ambry's XLID Next-Gen Panel™ utilizes massive parallel sequencing technology to detect point mutations, small insertions and deletions in 81 genes implicated in X-linked intellectual disability. 

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Ambry's XLID Next-Gen Panel™ utilizes massive parallel sequencing technology to detect point mutations, small insertions and deletions in 81 genes implicated in X-linked intellectual disability. 

X-linked intellectual disability (XLID) involves a complex collection of clinically and genetically diverse disorders.1 Diagnosis of XLID is based on three main criteria: onset of symptoms before the age of 18, intellectual abilities significantly lower than average, and reduced adaptive skills. More than 200 conditions linked to >90 genes on the X chromosome include XLID as part of the clinical phenotype. Pathogenic mutations in these genes can represent the underlying cause of XLID, further accompanied by other congenital anomalies, developmental delay and autistic like features.  Approximately 42% of patients with XLID are anticipated to have mutations in one of 81+ clinically available genes.2

Disease Name 
X-Linked Intellectual Disability
Disease Information 

Individuals with XLID tend to struggle in areas including communication, health, interpersonal/social skills, leisure, safety, self-guidance and care, school performance, and work.

XLID affects approximately 1/600-1/1000 males as well as a significant number of females. 

Testing Benefits & Indication 

The XLID Next-Gen Panel may be considered for any individual with idiopathic syndromic or non-syndromic mental retardation, developmental delay, and learning disabilities with or without congenital abnormalities. 

Prenatal testing is available for families in which a specific mutation in one of the 81 genes has been identified.

Test Description 

The Ambry XLID Next-Gen Panel is a comprehensive gene sequencing screen for 81 genes associated with X-linked intellectual disability (nonsyndromic and syndromic).  Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized kit and quantified by agarose gel electrophoresis. Sequence enrichment is carried out by incorporating the gDNA into microdroplets along with primer pairs designed to the target XLID gene coding exons followed by polymerase chain reaction (PCR) and Next-Gen Sequencing. Additional Sanger sequencing is performed for any regions missing coverage, and for any regions with sequence similarity elsewhere in the genome (including exons of genes as noted in individual gene test entries). Suspect variant calls other than those classified as "likely benign" or "benign" are verified by sanger sequencing in sense and antisense directions.

The Ambry XLID Next-Gen Panel™ targets detection of mutations in  81 genes by either Next-Generation or Sanger sequencing of all coding domains plus at least 10 bases into the 5’ and 3’ ends of all the introns. The following sites are used to search for previously described XLID mutations and polymorphisms: Human Gene Mutation Database (HGMD) and online search engines (e.g., OMIM, PubMed).

Mutation Detection Rate 

Clinical sensitivity: Approximately 42% of patients with a family history of XLID are anticipated to have mutations in one of the 81+ known genes implicated in XLID4.

Analytic sensitivity: The Ambry XLID Next-Gen Panel™ is designed and validated to be capable of detecting 83% of described mutations in the 81 genes represented on the panel (considering less than 17% to be the other types of mutations).

Specimen Requirements 

Blood: 5-10 cc blood in purple top EDTA tube (preferred) or yellow top citric acetate tube.
Storage: 2-8°C. Do not freeze.
Shipment: Room temperature for two-day delivery.
DNA: 25μg of of DNA in TE (10mM Tris-Cl pH 8.0, 1mM EDTA); Minimum concentration 50 ng/μl.
Storage: -20°C.
Shipment: Shipment frozen on dry ice is preferred, or ship on ice.

Turnaround Time 
Technique Days
XLID Next-Gen Panel 84-112

 

Specialty 
References 

1. Gecz J et al. The genetic landscape of intellectual disability arising from chromosome X. Trends in Genetics. 2009;25(7):308-316. [PMID: 19556021]

4. de Brouwer et al. Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium. Hum Mutation. 2007:28(2):207-8. [PMID: 17221867]