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Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder. It is characterized by focal development and progressive enlargement of renal cysts leading to end-stage renal disease. PKD1 and PKD2 have been implicated in ADPKD pathogenesis but genetic features and the size of PKD1 make genetic diagnosis tedious. Methods We aim to prove that high resolution melt analysis (HRM), a recent technique in molecular biology, can facilitate molecular diagnosis of ADPKD. We screened for mutations in PKD1 and PKD2 with HRM in 37 unrelated patients with ADPKD. Results We identified 440 sequence variants in the 37 patients. One hundred and thirty eight were different. We found 28 pathogenic mutations (25 in PKD1 and 3 in PKD2 ) within 28 different patients, which is a diagnosis rate of 75% consistent with literature mean direct sequencing diagnosis rate. We describe 52 new sequence variants in PKD1 and two in PKD2. Conclusion HRM analysis is a sensitive and specific method for molecular diagnosis of ADPKD. HRM analysis is also costless and time sparing. Thus, this method is efficient and might be used for mutation pre-screening in ADPKD genes.

Microdeletions in the chromosomal region 17p13.3 are associated with neuronal migration disorders, and PAFAB1H1 is the main gene involved. The largest genomic imbalances, including the YWHAE and CRK genes, cause more severe structural abnormalities of the brain and other associated dysmorphic features. Here, we describe a 3-year-old boy with a microdeletion in 17p13.3 presenting with minor facial dysmorphisms, a cleft palate, neurodevelopmental delay, and behavioral disorder with no structural malformation of the brain. The patient was evaluated by a clinician using a standard protocol. Laboratory investigation included GTG-banding, whole-genome AGH, and array-CGH. Whole-genome AGH and array-CGH analysis identified an estimated 2.1-Mb deletion in the 17p13.3 region showing haploinsufficiency of the YWHAE , CRK , H1C1 , and OVCA1 genes and no deletion of PAFAH1B1 . The complex gene interaction on brain development and function is illustrated in the genotype-phenotype correlation described here. This report reinforces the importance of the 17p13.3 region in developmental abnormalities and highlights the weak implication of the HIC1 and OVCA1 genes in palatogenesis.

This article reports a patient with a de novo ∼ 9.32 Mb duplication at 16p13.3 and a ∼ 71 Kb deletion at 22q13.33. The patient was followed from 1 month old to 3 years and 8 months of age and presented typical features of the 16p13.3 duplication syndrome. In addition, the patient presents a portal cavernoma, an alteration rarely reported in this condition. Renal agenesis was detected as additional developmental defect. After genomic array and FISH analysis, the karyotype was 46,XX,ins(22;16)(q13;p13.2p13.3). ish ins(22;16)(RP11-35P16+, RP11-27M24+). arr16p13.2p13.3(85,880-9,413,353)×3 dn arr22q13.33 (51,140,789-51,197,838)×1 dn. The authors provide a comprehensive review of the literature. This approach shed light on the genotype-phenotype correlation., (© 2015 Wiley Periodicals, Inc.)

Objectives: To describe prevalence of associated defects and clinical-genetic characteristics of patients with typical orofacial clefts seen at a reference genetic service., Methods: Descriptive study conducted between September of 2009 and July of 2014. Two experienced dysmorphologists personally collected and coded clinical data using a validated, standard multicenter protocol. Syndromic cases were defined by the presence of four or more minor defects, one or more major defects, or recognition of a specific syndrome. Fisher's exact and Kruskal-Wallis tests were used for statistics., Results: Among 141 subjects, associated defects were found in 133 (93%), and 84 (59.5%) were assigned as syndromic. Cleft palate was statistically associated with a greater number of minor defects (p<0.0012) and syndromic assignment (p<0.001). Syndromic group was associated with low birth weight (p<0.04) and less access to surgical treatment (p<0.002). There was no statistical difference between syndromic and non-syndromic groups regarding gender (p<0.55), maternal age of 35 years and above (p<0.50), alcohol (p<0.50) and tobacco consumption (p<0.11), consanguinity (p<0.59), recurrence (p<0.08), average number of pregnancies (p<0.32), and offspring (p<0.35)., Conclusions: There is a lack of information on syndromic clefts. The classification system for phenotype assignment adopted in this study has facilitated recognition of high prevalence of associated defects and syndromic cases. This system may be a useful strategy to gather homogeneous samples, to elect appropriate technologies for etiologic and genotype-phenotype approaches, and to assist with multiprofessional care and genetic counseling., (Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

In this study, 103 unrelated South-American patients with mucopolysaccharidosis type II (MPS II) were investigated aiming at the identification of iduronate-2-sulfatase (IDS) disease causing mutations and the possibility of some insights on the genotype-phenotype correlation The strategy used for genotyping involved the identification of the previously reported inversion/disruption of the IDS gene by PCR and screening for other mutations by PCR/SSCP. The exons with altered mobility on SSCP were sequenced, as well as all the exons of patients with no SSCP alteration. By using this strategy, we were able to find the pathogenic mutation in all patients. Alterations such as inversion/disruption and partial/total deletions of the IDS gene were found in 20/103 (19%) patients. Small insertions/deletions/indels (<22 bp) and point mutations were identified in 83/103 (88%) patients, including 30 novel mutations; except for a higher frequency of small duplications in relation to small deletions, the frequencies of major and minor alterations found in our sample are in accordance with those described in the literature., (© 2013.)

The 22q11.2 deletion is the most frequent interstitial deletion in humans and presents a wide phenotypic spectrum, with over 180 clinical manifestations described. Distinct studies have detected frequencies of the deletion ranging from 0 % to 75 %, depending on the studied population and selection criteria adopted. Due to the lack of consensus in this matter, several studies have been conducted aiming to define which patients would be eligible for screening; however, the issue is still up for debate. In order to contribute to the delineation of possible clinical and dysmorphologic guidelines to optimize decision making in the clinical setting, 194 individuals with variable features of the 22q11.2 deletion syndromes (22q11.2DS) were evaluated. Group I, clinical suspicion of 22q11.2DS with palatal anomalies; Group II, clinical suspicion without palatal anomalies; Group III, cardiac malformations associated with the 22q11.2DS; and Group IV, juvenile-onset schizophrenia. Multiplex ligation-dependent probe amplification was used for screening the 22q11.2 deletion, which was detected in 45 patients (23.2 %), distributed as such: Group I, 35/101 (34.7 %); Group II, 4/18 (22.2 %); Group III, 6/52 (11.5 %); and Group IV, 0/23 (0 %). Clinical data were analyzed by frequency distribution and statistically. Based on the present results and on the review of the literature, we propose a set of guidelines for screening patients with distinct manifestations of the 22q11.2DS in order to maximize resources. In addition, we report the dysmorphic features which we found to be statistically correlated with the presence of the 22q11.2DS.

Because of the restricted intake of high-biologic-value protein, children with phenylketonuria (PKU) may have lower than normal plasma concentrations of copper, zinc, and selenium. The purpose of the present study was to investigate erythrocyte zinc levels and serum copper and selenium levels in children and adolescents with PKU by analyzing the relation between their diet and the laboratory profiles of these elements. The study was conducted in 32 children and adolescents with PKU, who were on a special diet. Dietary records and blood samples were collected from each subject. Erythrocyte zinc and serum selenium levels were below normal in 37.5% and 90.6% of the subjects, respectively. Plasma copper levels were normal. Metabolic formulas were the only source of 86.9% of the zinc, 65.6% of the copper, and 32.4% of the selenium. Despite this, there was no significant correlation between the zinc formula supply and erythrocyte zinc levels (rho = -0.143, P = .435) or the supply and serum levels for copper (rho = -0.117, P = .523) and selenium (rho = 0.113, P = .538). These results suggest that Brazilian patients with PKU present with low ingestion levels, low serum selenium levels, and low erythrocyte zinc levels.