In this paper we review same results obtained from the AIP and VP families studied at biochemical and molecular level at the CIPYP in Argentina.Taking into account the relationship between the porphyric attack and oxidative stress, we also decided to study oxidative stress parameters and homocysteine levels in AHP patients and controls, to identify a marker of neurological dysfunction.

The rare hereditary disease with complex arrhythmia syndrome resulted from the heterozygous linkage SCN5A R965C-R1309H mutation, detected by targeted capture sequencing. The linkage mutation SCN5A R965C-R1309H led to a more dramatic reduction in the current density of sodium channel, more depolarisation-shifted activation and more hyperpolarisation-shifted inactivation than either single mutation, R965C or R1309H, indicating synergistic effects on the pore-gating properties of sodium channels, as detected by whole-cell recordings.

In this study we report our experience with gene mutations in children suspected to have Stickler syndrome type collagenopathy based on ocular examination.To the best of our knowledge this is the first such study based on ascertainment by an ophthalmologist.

Synonymousmutation can cause skipping of exon in the RNA transcript, thus resulting in the production of mutant α2(V)-chains and clinical phenotype of classical Ehlers-Danlos syndrome. Our results highlights the need to include splicing-altering synonymous mutations into the screening for cEDS.

In this study we have used an Next Generation Sequencing (NGS) panel covering the whole DMD gene to identify mutations in the 24 DMD patients and their matriliniage for up to four generations.

Although distinctive facial features have been reported between Noonan and Williams–Beuren syndromes, studies have found a variable incidence of those characteristics in populations with diverse ancestry. We sought to identify and quantify facial features discriminative of these two syndromes in population with diverse ancestry using facial analysis. We provide for the first time quantitative reference facial metrics in diverse populations that can be used both at the clinic and for training purposes.

A Chinese patient bearing with a novel NF1 mutation is involved in this study. The present complaint of this patient is bone phenotype including short stature and scoliosis. Functional studies confirm that this novel mutant could active Ras/Erk signaling and perhaps further inhibit the development of osteoblasts (OBLs), which provide a potential molecular mechanism to explain the bone maldevelopment of patients with neurofibromatosis type 1.

A new mutation of the CD40 ligand gene (CD40LG) that encodes the CD40 ligand (CD40L) molecule was detected in a 20-month-old boy harbouring an X-linked hyper-IgM syndrome (X-HIGM) combined with immunodeficiency syndrome. Inactivation of the CD40LG gene resulted from the insertion of mitochondrial DNA copies into exon 1, which in turn led to a total deficiency of CD40L expression of T lymphocytes.

Prenatal CNS anomalies (mainly ventriculomegaly) at third trimester, should be considered a prenatal ultrasound marker of this syndrome. This kind of malformations raise the possibility of an underlying genetic condition including 17q21.31 microdeletion. Thus CMA should be taken into consideration when offering prenatal genetic counselling.

Whole-exome sequencing analysis, ten families of sporadic microtia; microtia with thoracic deformities.

This study describes the association of a genetic Podocalyxin (PODXL) variant with a familial glomerular nephropathy characterized by focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis features. This finding expands the phenotypic spectrum associated to PODXL variants and highlights the importance to screen the PODXL gene for deleterious variants in similar disease forms.

Although enzyme replacement therapy with agalsidase beta resulted in a variety of clinical benefits, life-long biweekly intravenous infusion may impact on patients’ quality of life because regular infusions are time-consuming. In this study, we reported our experience with a stepwise infusion rate escalation protocol developed in our center in a cohort of 53 Fabry patients (both already receiving and treatment-naΪve), and explored factors predictive for the infusion rate increase tolerability. We showed that our infusion rate escalation protocol is safe and could improve patient compliance, satisfaction and quality of life.

Patients’ perception of collaboration between clinical departments and being married raise SWLS scores.

NGS-based PGT is an effective strategy for the detection of monogenic diseases resulting from mosaicism. Furthermore, NGS-based PGT combined with PB genetic analysis can improve the accuracy of PGT for monogenic diseases due to maternal mosaicism. This approach will assist clinicians to undertake a more objective assessment of disease recurrence risk for mosaic individuals and obtain an accurate diagnosis of the genotype of embryos for reproductive interventions.

There are no quantitative data on the risk that parents or adults with Duchenne would accept for a non-curative gene therapy. We used a survey with threshold technique and a hypothetical treatment vignette to measure maximum acceptable risk (MAR) for death at four timepoints in the life of the person with Duchenne. We find relatively high tolerance for mortality risk that increases with progression. Patients and caregivers overall showed a willingness to accept risk and uncertainty in exchange for the hypothetical benefit profile presented.

This study characterized a novel COL10A1 variant (c.1863_1866delAATG, p.M622 Tfs*54) associated with Schmid type metaphyseal chondrodysplasia in a two-year-old Chinese patient. The novel variant was predicted to impair the trimerization of collagen X (α1) and combination with molecules in the matrix by in silico analysis. The NC1 domain of COL10A1 was a key region underlying SMCD, patients with NC1 mutations tend to present severer manifestations at earlier age.

Rare diseases present several difficulties for patients, from the delay in the diagnosis to the lack of treatments. Next generation sequencing techniques have improved the search for diagnosis in several such pathologies. Here, we present the case of an undiagnosed six years old boy with severe encephalopathy of unclear cause, whose etiological diagnosis was achieved by whole genome sequencing.

We studied a large family with 22 individuals affected with autosomal dominant hereditary spherocytosis (HS). Genome-wide linkage and whole-genome sequencing analyses revealed a heterozygous G>A transition in the 14q23 locus, at position +1 of the intron 8 donor splice site of the spectrin beta, erythrocytic (SPTB) gene.

We report the endocrinological features of a male patient with 14q microdeletion and Dubowitz phenotype who showed a good response to short-term GH therapy.

We report a family in which the members have various genetic states and manifestations of PFBC. Notably, the proband carrying the SLC20A2 and PDGFRB heterozygous mutations showed more severe brain calcification and earlier onset age of clinical symptoms than her family members, highlighting digenic influences on the characteristics of PFBC patients.

MPSS based-NIPT can be considered as performant for the detection of 45,X in high-risk pregnancies, although this result is based on studies that might contain biases. For the other SCAs including 47,XXX, 47,XXY, and 47,XYY, more quality studies are still needed.

This review article discusses the literature published on family genetic testing for Fabry disease and the experiences of 19 Fabry experts from 15 countries regarding family screening in their countries and the barriers they are facing. Together, this literature overview and combined global experience provides valuable insights to medical geneticists working to improve the diagnosis of rare diseases within their countries and globally.