Duplication of 14q11.2 associates with short stature and mild mental retardation: a putative relation with quantitative trait loci.
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Aneuploidy↗
Biomedical subjects
Sandra Monfort
Publications and source records attributed to Sandra Monfort.
A subtelomeric translocation apparently implied in multiple abortions.
PURPOSE: Chromosomal alterations are a major cause of clinically recognized abortions. So cryptic chromosomal rearrangements could be responsible for recurrent miscarriages. METHODS: The study was performed on 18 clinically normal couples who had four or more spontaneous abortions and whose karyotypes were found to be normal. Fluorescence in situ hybridization with specific probes of subtelomeric regions was used after optimizing the amount of probe. RESULTS: Only one subtelomeric translocation was detected between 2p and 3p chromosomes, in a female with seven miscarriages. CONCLUSION: Subtelomeric rearrangements are infrequently related to multiple miscarriages. This kind of studies can be considered specially worthy when a couple have had not only abortions but also offspring with mental and physical anomalies. Thus, possible initial studies should focus on affected children or fetus.
Abortion, Habitual↗
Evaluation of MLPA for the detection of cryptic subtelomeric rearrangements.
Chromosomal rearrangements involving the telomeres are implied as a significant cause of idiopathic mental retardation. The most frequently used technique to detect these rearrangements was fluorescent in situ hybridization (FISH), an expensive and labor-intensive technique. One of the most promising alternative techniques is multiplex ligation-dependent probe amplification (MLPA). Here, the authors present the evaluation of a double set of probes (the SALSA P036, P019, and P020 human telomere test kits) on a series of 95 patients and 22 normal controls. Overall, 34 patients had been studied by telomeric FISH and MLPA, which was demonstrated to be a reliable method to detect essentially all subtelomeric rearrangements characterized by FISH. In addition, in these 34 patients, 13 dose imbalances were detected by MLPA, but not by FISH analysis. Overall, 12 alterations were observed only with one of the two sets, and they corresponded to polymorphic variants, as they were inherited from healthy parents or also appear in normal controls. The remaining 61 patients were initially studied with SALSA P036, and any putative dose alteration was confirmed with the two other kits and FISH. In the whole series, the authors found 9 dose imbalances evidenced with 2 MLPA kits and confirmed by FISH, representing 10% of patients with subtelomeric rearrangements. On the other hand, one small duplication at 14q11 may be clinically relevant as it appears de novo in one patient. In conclusion, MLPA can be considered a quick, sensitive, cost-effective, and easy method to screen for subtelomeric rearrangements, but any finding based in the testing of one probe should be confirmed by other sources.
Chromosome Deletion↗
Robust, easy, and dose-sensitive methylation test for the diagnosis of Prader-Willi and Angelman syndromes.
We present a new method for differential diagnosis of Prader-Willi (PWS) and Angelman syndromes (AS) that requires only a small amount of DNA including that obtained from amniocentesis specimens. This method not only proved to be robust and rapid, but, most importantly, it can be dosage sensitive, supplying additional information useful for genetic counselling. After methylation-dependent digestion of DNA with HpaII or McrBC, exon 1 of the SNRPN gene is amplified together with a sequence in the CpG island of the H19 gene. Given the similarities in sequence composition and methylation status between the amplified sequences, their co-amplification under semiquantitative conditions allows an easy discrimination between single dosage (present in deletions or chromosomal translocations) and a double-dosage state (uniparental disomy or imprinting error), when the appropriate controls are included. The method we have developed in combination with standard cytogenetic studies and segregation analysis of microsatellite markers offers a rapid and easy procedure to resolve most suspected cases of PWS and AS, and consequently to provide accurate genetic counselling.
Angelman Syndrome↗
Localization of MRX82: a new nonsyndromic X-linked mental retardation locus to Xq24-q25 in a Basque family.
Clinical and molecular studies are reported on a Basque family (MRX82) with nonsyndromic X-linked mental retardation (XLMR) in five affected males. A total of 38 microsatellite markers were typed. The XLMR locus has been linked to DXS8067, DXS1001, DXS425, DXS7877, and DXS1183 with a maximum LOD score of 2.4. The haplotype studies and multipoint linkage analysis suggest a localization of the MRX82 locus to an interval of 7.6 Mb defined by markers DXS6805 and DXS7346, in Xq24 and Xq25, respectively. No gene contained in this interval has been so far associated with nonsyndromic mental retardation, except for GRIA3, disrupted by a balanced translocation in a female patient with bipolar affective disorder and mental retardation. However, the search for mutations of this gene did not showed a pathogenic mutation in the present family. Given that there are other eight MRX families overlapping this interval, none of them with known mutation, we conclude that at least one new gene responsible for nonsyndromic mental retardation is located in this region.
Chromosome Mapping↗