Abstract：
BACKGROUND:FMR1 full mutations (FMs) (CGG expansion >200) in males mosaic for a normal (<45 CGG) or gray-zone (GZ) (45-54 CGG) allele can be missed with the standard 2-step fragile X syndrome (FXS) testing protocols, largely because the first-line PCR tests showing a normal or GZ allele are not reflexed to the second-line test that can detect FM. METHODS:We used methylation-specific quantitative melt analysis (MS-QMA) to determine the prevalence of cryptic FM alleles in 2 independent cohorts of male patients (994 from Chile and 2392 from Australia) referred for FXS testing from 2006 to 2013. All MS-QMA-positive cases were retested with commercial triplet primed PCR, methylation-sensitive Southern blot, and a methylation-specific EpiTYPER-based test. RESULTS:All 38 FMs detected with the standard 2-step protocol were detected with MS-QMA. However, MS-QMA identified methylation mosaicism in an additional 15% and 11% of patients in the Chilean and Australian cohorts, respectively, suggesting the presence of a cryptic FM. Of these additional patients, 57% were confirmed to carry cryptic expanded alleles in blood, buccal mucosa, or saliva samples. Further confirmation was provided by identifying premutation (CGG 55-199) alleles in mothers of probands with methylation-sensitive Southern blot. Neurocognitive assessments showed that low-level mosaicism for cryptic FM alleles was associated with cognitive impairment or autism. CONCLUSIONS:A substantial number of mosaic FM males who have cognitive impairment or autism are not diagnosed with the currently recommended 2-step testing protocol and can be identified with MS-QMA as a first-line test.
journal_name
Clin Chemjournal_title
Clinical chemistryauthors
Aliaga SM,Slater HR,Francis D,Du Sart D,Li X,Amor DJ,Alliende AM,Santa Maria L,Faundes V,Morales P,Trigo C,Salas I,Curotto B,Godler DEdoi
10.1373/clinchem.2015.244681subject
Has Abstractpub_date
2016-02-01 00:00:00pages
343-52issue
2eissn
0009-9147issn
1530-8561pii
clinchem.2015.244681journal_volume
62pub_type
杂志文章abstract：:We compared relative increases in creatine kinase (EC 2.7.3.2) MB isoenzyme (CK-MB) after reperfusion in myocardial infarction for four popular methods: electrophoresis, immunoinhibition, the "Magic Lite" (Ciba-Corning) system, and the Stratus (Dade). In a method comparison study, we confirmed that all four methods co...
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