Background:
Syndromic and non-syndromic intellectual disability associated with genes on the X chromosome account for approximately 5% of intellectual disability (ID) in males; prevalence of X-linked ID is approximately 1/600-1000 for males (Lubs et al. 2012AJHG 90; Gecz et al. 2009 Trends Genet 25). Most cases are non-syndromic, with few other features to aid in diagnosis. Thus, screening large sets of genes on the X chromosome for sequence-level mutations provides a rapid and cost-effective method to detect changes in genes that can contribute to X-linked intellectual disability, particularly when family history suggests an X-linked inheritance pattern. The current panel comprises 88 genes on the X chromosome that have been associated with ID.
Reasons for Referral:
- Negative Fragile X testing (in males) and negative chromosomal microarray testing*
- Unexplained intellectual disability
- Familial intellectual disability with inheritance patterns suggestive of X-linked transmission
*Tests for Fragile X and for submicroscopic regional copy number gains and losses (chromosomal microarray) are available in our laboratory and may require additional specimen. It is recommended that these tests be performed before the sequencing and del/dup panel(s). Please contact our lab for more information.
Methodology:
Next generation sequencing will analyze the exons or coding regions of 88 X-linked Intellectual Disability genes using Illumina NextSeq 500 technology and preparing samples using hybridization probes to enrich exonic regions. Any gaps in coverage in clinically validated genes are completed with traditional Sanger sequencing such that 100% of the coding region of the above genes are covered at 10x coverage or more. Promoter, intronic, etc. regions are not assessed here but may contain variants that impact gene function.
X-Linked Intellectual Disabilities Panel (88 genes): ACSL4, AFF2, AP1S2, ARHGEF9, ARX, ATP6AP2, ATP7A, ATRX, BCOR, BRWD3, CASK, CCDC22, CDKL5, CLIC2, CNKSR2, CUL4B, DCX, DKC1, DLG3, DMD, FANCB, FGD1, FLNA, FMR1, FRMPD4, FTSJ1, GDI1, GK, GPC3, GRIA3, HCCS, HPRT1, HSD17B10, HUWE1, IDS, IGBP1, IL1RAPL1, IQSEC2, KDM5C, KIAA2022, L1CAM, LAMP2, MAOA, MBTPS2, MECP2, MED12, MID1, NAA10, NDP, NDUFA1, NHS, NLGN3, NLGN4X, NSDHL, OCRL, OFD1, OPHN1, OTC, PAK3, PCDH19, PDHA1, PGK1, PHF6, PHF8, PLP1, PORCN, PQBP1, PRPS1, PTCHD1, RAB39B, RBM10, RPL10, RPS6KA3, SHROOM4, SLC16A2, SLC9A6, SMC1A, SMS, SOX3, SYN1, SYP, TIMM8A, TSPAN7, UBE2A, UPF3B, ZDHHC15, ZDHHC9, ZNF711
KDL also offers deletion/duplication analysis for the 88 X-linked Intellectual Disability genes. Please contact Client Services at (855) 535-1522 for more information.
Specimen Requirements:
Blood: EDTA or ACD (Solution A or B):
- Adult: 5 mL
- Child: 5 mL
- Infant: 2-3 mL
A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES. Please include detailed clinical information, including ethnicity, clinical history, and family history.
Test Performed (Days):
Weekly
Turn Around Time:
8 weeks
Shipment Sensitivity Requirements:
- Package and ship specimen to remain cold, but not frozen.
- Ship via overnight express, using the FedEx priority overnight label provided.
- Contact Client Services for shipping kits and instructions at (855) 535-1522.
References:
Additional Info: