engleski

Screening of patients with mental retardation using subtelomeric MLPA assay

Subtelomeric imbalances are a significant cause of mental retardation/developmental delays (MR/DD) in patients with or without phenotypic abnormalities. Multiplex ligation-dependent probe amplification (MLPA) is relatively low cost, rapid, and high throughput prospective screening tool for copy number quantification. We developed a strategy of screening for chromosomal subtelomere imbalances with two MLPA kits followed by confirmation and delineation of breakpoints with selective telomere follow-up MLPA specific kits. We screened 105 patients with idiopathic MR/DD associated with dysmorphic features and/or malformations and normal karyotype using SALSA P036 and SALSA P070 MLPA kits. Subtelomeric anomalies were found in 10 patients (10/105 – 9.5%). Three were three de novo deletions (4p, 15q and 22q) one deletion and duplication at 19p, three duplications (X/Yp) and three deletions and duplications (dup3p/del18q, dup8p/del18q and del12p/dup22q) resulting from balanced parental reciprocal translocations. Telomere follow-up MLPA specific kits delineated the size of six (6/10 – 60%) subtelomeric abnormalities that ranged from 0, 5 to 6, 1 Mb. These imbalances were not visible on subsequent high resolution karyotyping (600 – 800 bands). High-resolution microscope analysis of involved chromosomes validated and further delineated subtelomeric abnormalities in three patients: del4q16.3dn, der(18)t(3 ; 18) (p26.1 ; q22.1)mat, der(18)t(8 ; 18)(p23.1 ; q22.1)pat. Their size ranged between 4, 5 and 13, 8 Mb. Presented diagnostic testing strategy increases significantly diagnostic detection rate of subtelomeric imbalances in patients with idiopathic mental retardation. Our survey confirms the observation that subtelomeric rearrangements are a significant cause of idiopathic MR.

mental retardation ; MLPA

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