Sebastian A. Vishnopolska

Universidad de Buenos Aires | UBA

Patients with Inborn Errors of Immunity (IEI) in Argentina were encouraged to receive licensed Sputnik, AstraZeneca, Sinopharm, Moderna, and Pfizer vaccines, even though most of the data on available vaccines comes from trials conducted in healthy individuals. We aimed to evaluate the safety and immunogenicity of the different vaccines in IEI patie...

Pituitary hormone deficiency occurs in ∼1:4,000 live births. Approximately 3% of the cases are due to mutations in the alpha isoform of POU1F1, a pituitary-specific transcriptional activator. We found four separate heterozygous missense variants in unrelated individuals with hypopituitarism that were predicted to affect a minor isoform, POU1F1 beta...

Pituitary hormone deficiency or hypopituitarism is characterized by a malformed or underdeveloped pituitary gland resulting in an impaired pituitary hormone secretion. Several transcription factors have been described in its etiology, but defects in known genes account for only a small proportion of cases. We sought to identify the cause of hypopit...

Congenital hypopituitarism (CH), septo-optic dysplasia (SOD), and holoprosencephaly (HPE) constitute an important group of structural birth defects that cause significant morbidity and life-long consequences for quality of life and care. The genetic causes are highly overlapping. As such, these disorders can be considered as a spectrum of related d...

Purpose Congenital hypopituitarism (CH) can present in isolation or with other birth defects. Mutations in multiple genes can cause CH, and the use of a genetic screening panel could establish the prevalence of mutations in known and candidate genes for this disorder. It could also increase the proportion of patients that receive a genetic diagnosi...

Background: Oculocutaneous albinism (OCA) is a Mendelian disorder characterized by hypopigmentation of the skin, hair, and eyes, hypoplastic fovea, and low vision, known to be caused by mutations in the Tyrosinase (TYR) gene. Among the known TYR variants, some reduce but do not completely eliminate tyrosinase activity, allowing residual production...

Pituitary hormone deficiency occurs in ~1:4,000 live births. Approximately 3% of the cases are due to mutations in the alpha isoform of POU1F1, a pituitary-specific transcriptional activator. We found four separate heterozygous missense variants in unrelated hypopituitarism patients that were predicted to affect a minor isoform, POU1F1 beta, which...

The anterior pituitary gland is comprised of specialized cell-types that produce and secrete polypeptide hormones in response to hypothalamic input and feedback from target organs. These specialized cells arise during embryonic development, from stem cells that express SOX2 and the pituitary transcription factor PROP1, which is necessary to establi...

Combined pituitary hormone deficiency (CPHD) is an important clinical problem caused by mutations in more than 30 different genes. Six genes in the Sonic Hedgehog (SHH) signalling pathway are reported to cause CPHD. SHH signaling is essential to induce pituitary cell identity in cells of Rathke’s pouch by stimulating expression of the transcription...

Objective: to describe the marked variability in clinical and biochemical patterns that are associated with a p.R209H GH1 missense variant in a large Argentinean pedigree, which makes the diagnosis of GHD elusive. Design: We describe a non-consanguineous pedigree composed by several individuals with short stature, including 2 pediatric patients...

Isolated growth hormone deficiency (IGHD) is most frequently caused by mutations in the GH1 gene. Pathogenic mutations in the GHRHR and GHSR have also been reported to cause IGHD. Individuals with IGHD type II present with variable clinical phenotype. Autosomal dominant GH1 p.R209H variant impairs GH secretion despite normal GH synthesis. The aim o...

Congenital hypopituitarism occurs in 1/3,000 - 1/10,000 live births and is highly variable phenotypically. The condition is life-long and life-threatening if untreated. Diagnosis remains a challenge, particularly in the neonatal period. There is a need for better diagnosis that would lead to improved prognosis and treatment. We recently implemented...

Understanding the functional effect of Single Amino acid Substitutions (SAS), derived from the occurrence of single nucleotide variants (SNVs), and their relation to disease development is a major issue in clinical genomics. Despite the existence of several bioinformatic algorithms and servers that predict if a SAS is pathogenic or not, they give l...

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A historical summary of genetics and genomic medicine in Argentina. We go through the achievements and difficulties in the implementation of genetic and genomic services both in academia and health care.

Background Congenital Hypopituitarism is caused by genetic and environmental factors. Over 30 genes have been implicated in isolated and/or combined pituitary hormone deficiency. The etiology remains unknown for up to 80% of the patients, but most cases have been analyzed by limited candidate gene screening. Mutations in the PROP1 gene are the most...

Understanding the functional effect of Single Amino acid Substitutions (SAS), derived from the occurrence of single nucleotide variants (SNVs), and their relation to disease development is a major issue in clinical genomics. Even though there are several bioinformatic algorithms and servers that predict if a SAS can be pathogenic or not they give l...

Neuronal migration disorders are a clinically and genetically heterogeneous group of malformations of cortical development, frequently responsible for severe disability. Despite the increasing knowledge of the molecular mechanisms underlying this group of diseases, their genetic diagnosis remains unattainable in a high proportion of cases. Here, we...

Phenotypic characteristics of the NMD cohort. (XLSX)

Somatic mutations. NGS data, in silico analysis of pathogenicity and population frequency is shown for pathogenic or likely pathogenic variants. (XLSX)

Germinal novel mutations. In silico analysis of pathogenicity. (XLSX)

Somatic mutations: Intraexonic deletion of patient MDC 1092. A Targeted high coverage NGS. Exon 2 of patient MDC 1092 compared to normal exon 2 of patient MDC 1093. In patient 1092 the average coverage is significantly lower in the deleted fragment. B.Sanger sequencing after subcloning. (XLSX)

Sanger electropherogram confirming the NM_139058:c.1427_1428delTCinsAA; p.F476X in patient 1039 (male). As ARX is located in the X chromosome only one allele is represented. (XLSX)

Somatic mutations: Sanger sequencing after subcloning. Individuals MDC 1070 and MDC 1093. (XLSX)