Search

A letter to the editor is presented about the unbalanced subtelomeric rearrangements that are significant cause of syndromic mental retardation in the previous issue.

Aller E, Jaijo T, Oltra S, Alió J, Galán F, Nájera C, Beneyto M, Millán JM. Mutation screening ofUSH3gene (clarin-1) in Spanish patients with Usher syndrome: low prevalence and phenotypic variability.Usher syndrome type III is an autosomal recessive disorder clinically characterized by the association of retinitis pigmentosa (RP), variable presence of vestibular dysfunction and progressive hearing loss, being the progression of the hearing impairment the critical parameter classically used to distinguish this form from Usher syndrome type I and Usher syndrome type II. Usher syndrome type III clinical subtype is the rarest form of Usher syndrome in Spain, accounting only for 6% of all Usher syndrome Spanish cases. The gene responsible for Usher syndrome type III is namedclarin-1and it is thought to be involved in hair cell and photoreceptor cell synapses. Here, we report a screening for mutations inclarin-1gene among our series of Usher syndrome Spanish patients.Clarin-1has been found to be responsible for the disease in only two families: the first one is a previously reported family homozygous for Y63X mutation and the second one, described here, is homozygous for C40G. This accounts for 1.7% of Usher syndrome Spanish families. It is noticeable that, whereas C40G family is clinically compatible with Usher syndrome type III due to the progression of the hearing loss, Y63X family could be diagnosed as Usher syndrome type I because the hearing impairment is profound and stable. Thus, we consider that the progression of hearing loss is not the definitive key parameter to distinguish Usher syndrome type III from Usher syndrome type I and Usher syndrome type II. [ABSTRACT FROM AUTHOR]

Two novel mutations of the ribosomal S6 kinase 2 gene (also known as RSK2) have been identified in two unrelated patients with Coffin Lowry syndrome. The first mutation consists of a de novo insertion of a 5'truncated LINE-1 element at position -8 of intron 3, which leads to a skipping of exon 4, leading to a shift of the reading frame and a premature stop codon. The L1 fragment (2800 bp) showed a rearrangement with a small deletion, a partial inversion of the ORF 2, flanked by short direct repeats which duplicate the acceptor splice site. However, cDNA analysis of the patient shows that both sites are apparently not functional. The second family showed the nucleotide change 803T>C in exon 10, resulting in the F268S mutation. This mutation was detected in two monozygotic twin patients and in their mother, who was mildly affected. The patients fulfill the clinical criteria of the syndrome, and therefore the mutation provides further support for the importance of phenylalanine at position 268, which is highly conserved in the protein kinase domain of many serine-threonine protein kinases. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about a five-generation family with hypohidrotic ectodermal dysplasia.

Systematic reviews (SRs) and meta-analyses (MAs) are of great importance for basing clinical decisions. However, misleading interpretations may result when informed decisions rest on biased review papers with methodological issues. To evaluate which treatment is optimal, an overview was made of SRs and MAs to establish the quality and certainty of meta-evidence published on the efficacy of laser-based refractive surgery techniques for treating myopia in adults. A search was made in five databases and was updated using Really Simple Syndication (RSS) feed appliances up to April 2021; SRs with or without MAs were included. Methodological quality was appraised using the AMSTAR-2 tool. The best available reviews were summarized using the GRADE approach. The corrected covered area (CCA) was used to determine the degree of over-representation of publications. The risk of bias of the primary studies was disclosed visually. Thirty-six studies published between 2003 and 2021 were included. Twenty SRs (56%) were conducted in China. The most studied comparisons were SMILE versus FS-LASIK (19%) and FS-LASIK versus MM-LASIK (11%). Of the 251 overlapping index publications, 165 were unique (CCA = 0.015%), representing a negligible risk of skewed reporting. The AMSTAR-2 tool showed most SRs to have critically low or low quality. Nine reviews presented moderate quality. The GRADE approach of the 41 a priori outcomes evidenced critically low and low certainty of evidence. Only the spherical equivalent refraction changes at 12 months between LASEK and PRK showed moderate certainty of evidence, favouring PRK (mean difference 0.06, 95%CI [-0.02 to 0.14], I 2  = 0%; p ≥ 0.05). Index trials among less biased reviews are prone to selection, performance and reporting bias. The appraised techniques exhibit comparable results in terms of efficacy. There is moderate certainty of evidence in favour of the use of PRK over LASEK in terms of the spherical equivalent refraction error changes at 1 year of follow-up. Most appraised SRs presented methodological flaws in critical domains, resulting in a low to critically low certainty of evidence after GRADE appraisal. Therefore, investigators need to study and compare the different laser-based refractive techniques to provide better evidence-based medicine. Further well-designed, high-quality clinical trials and SRs are needed to reappraise the current findings., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Here we report on two unrelated male patients with syndromic intellectual disability (ID) due to duplication at Xq13.3-q21.1, a region of about 6 Mb and 25 genes. Among these, the most outstanding is ATRX, the causative gene of X-linked alpha-thalassemia/mental retardation. ATRX belongs to the growing list of genes implied in chromatin remodeling causing ID. Many these genes, such as MECP2, are dose-sensitive so that not only deletions and point mutations, but also duplications cause ID. Both patients have severe ID, absent expressive speech, early hypotonia, behavior problems (hyperactivity, repetitive self-stimulatory behavior), postnatal growth deficiency, microcephaly, micrognathia, cryptorchidism, low-set, posteriorly angulated ears, and downslanting palpebral fissures. These findings are also usually present among patients with loss-of-function mutations of the ATRX gene. Completely skewed X inactivation was observed in the only informative carrier mother, a constant finding among female carriers of inactivating point mutations of this gene. Participation of other duplicated genes cannot be excluded; nevertheless we propose that the increased dosage of ATRX is the major pathogenic mechanism of this X-linked disorder, a syndrome reminiscent of MECP2 duplication., (© 2014 Wiley Periodicals, Inc.)

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.