The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care

Kaul, Karen L.; Sabatini, Linda M.; Tsongalis, Gregory J.; Caliendo, Angela M.; Olsen, Randall J.; Ashwood, Edward R.; Bale, Sherri; Benirschke, Robert; Carlow, Dean; Funke, Birgit H.; Grody, Wayne W.; Hayden, Randall T.; Hegde, Madhuri; Lyon, Elaine; Murata, Kazunori; Pessin, Melissa; Press, Richard D.; Thomson, Richard B.

Fragile X (FX) syndrome is one of the most common inherited causes of intellectual disability. The causative molecular mechanism is an expansion of a CGG repeat region of the 5 0 regulatory region of the FMRP gene. When the CGG repeat expands beyond approximately 200 CGG repeats, the gene is methylated and silenced. Laboratory testing for FX includes sizing the number of repeats as well as methylation analysis and has been available for clinical diagnostic and carrier status testing for over 20 years. The American College of Medical Genetics and Genomics (ACMG) has published practice guidelines for appropriate test ordering. 97 It is a first tier test for individuals and families in which an X-linked inheritance pattern of intellectual disability is suspected. Once an expanded FX allele has been identified, other family members can be tested to identify premutation carriers at risk of having affected offspring. Prenatal (fetal) or preimplantation genetic diagnostic testing is available for known FX carriers.