Publications by authors named "Garcia-Arumi E"

Placental mesenchymal dysplasia (PMD) is a rare placental pathology that may be associated with Beckwith-Wiedemann features in the fetus and may be due to the presence of an androgenetic cell line. Many of the reported PMD cases describe the presence of a biparental and an isodisomic androgenetic cell line. The proposed mechanism of formation is by fertilization of a haploid ovum by a haploid sperm and duplication of the male pronucleus.

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Bainbridge-Ropers Syndrome (BRPS) is a genetic condition resulting from truncating variants in the ASXL3 gene. The clinical features include neurodevelopmental and language impairments, behavioral issues, hypotonia, feeding difficulties, and distinctive facial features. In this retrospective study, we analyzed 22 Spanish individuals with BRPS, aiming to perform a detailed clinical and molecular description and establish a genotype-phenotype correlation.

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Introduction/objective: Biallelic expansion of the pentanucleotide AAGGG in the RFC1- gene is associated with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study aimed to comprehensively characterise this condition by conducting an in-depth neurophysiological examination of afflicted patients.

Methods: A retrospective analysis was conducted in 31 RFC1-positive patients.

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  • The study investigates 11 previously unreported patients with a neurodevelopmental disorder (NDD) caused by genetic changes in the RNU4-2 gene, highlighting the need for better diagnostic approaches as many NDDs remain undiagnosed.
  • The patients, ranging from 13 months to 36 years old, exhibited severe developmental delays, distinct physical features, and other health issues like microcephaly and intrauterine growth retardation.
  • The findings enhance the understanding of RNU4-2 syndrome's phenotypic spectrum, emphasizing the importance of thorough clinical evaluations in identifying and characterizing new syndromes in patients with NDDs.
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  • Genetic defects in the TSH receptor can lead to various thyroid issues, such as thyroid dysgenesis or dyshormonogenesis, resulting in a wide range of symptoms from severe congenital hypothyroidism to mild hormonal imbalances.
  • A study analyzed 160 pediatric patients with thyroid dyshormonogenesis using high-throughput gene panels and in vitro tests to assess the impact of recognized genetic variants on thyroid function.
  • The findings showed that out of the patients studied, 3.13% had significant genetic variants affecting their thyroid health, with different variants exhibiting varying levels of functional impact, underscoring the necessity of genetic testing for accurate diagnosis.
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Thyroid dyshormonogenesis (THD) is a heterogeneous group of genetic diseases caused by the total or partial defect in the synthesis or secretion of thyroid hormones. Genetic variants in can cause partial to total iodination organification defects and clinical heterogeneity, from transient to permanent congenital hypothyroidism. The aim of this study was to undertake a molecular characterization and genotype-phenotype correlation in patients with THD and candidate variants in .

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: Non-Invasive prenatal test (NIPT) is used as a universal or contingent test after prior risk assessment. Screening is mainly performed for common trisomies (T21, T13, T18), although other chromosomal anomalies may be detected. Our objective was to study the performance of GWNIPT in the detection of chromosomal abnormalities in pregnancies in which an invasive prenatal study was performed and in early pregnancy losses, in comparison with the reference test.

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  • Palmoplantar keratoderma (PPK) is a skin condition that causes thick skin and abrasions on the hands and feet, linked to genetic factors, including mutations in a specific gene.
  • A new harmful variant (c.794G>C, p.Arg265Pro) in this gene was found in a 60-year-old female PPK patient, who had various symptoms such as skin changes, brittle nails, and thin hair.
  • This study suggests that the identified gene variant affects the stability of a protein crucial for WNT signaling, which is important for skin health, indicating that disrupted signaling may contribute to the development of PPK in the patient.
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Introduction: Defects in any thyroid hormone synthesis steps cause thyroid dyshormonogenesis (THD). THD due to () gene variants is a cause of congenital hypothyroidism (CH) with a wide clinical spectrum, ranging from mild to severe permanent hypothyroidism. We present high-throughput sequencing results of patients with variants.

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  • Previous studies showed high but varied levels of urine metabolites related to prostaglandins in cystic fibrosis patients, prompting this study to evaluate genetic factors affecting prostaglandin production and their potential as severity markers.
  • The research involved 30 healthy individuals and 103 cystic fibrosis patients, analyzing urine metabolites and clinical severity through scoring and CT scans.
  • Results indicated higher urinary levels of prostaglandin metabolites in cystic fibrosis patients compared to controls, with significant variations based on disease severity, but identified genetic polymorphisms did not correlate with disease severity or urine metabolite levels.
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Objectives: Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive disorder that stems from a perturbation of the mitochondrial DNA maintenance. Nucleoside treatment has recently shown promise as a disease-modifying therapy. TK2d was initially associated with rapidly progressive fatal myopathy in children featuring mitochondrial DNA depletion.

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  • - Tuberous sclerosis complex (TSC) is a genetic disorder causing hamartomas in various organs and is linked to mutations in the TSC1 and TSC2 genes, with many cases remaining undiagnosed despite genetic testing.
  • - The authors developed a comprehensive diagnostic method combining multiplex ligation-dependent probe amplification and advanced next-generation sequencing to better identify genetic variants in TSC patients.
  • - Their approach successfully identified the molecular cause in 29 out of 42 patients, including 12 new pathogenic variants, and highlighted the presence of low-frequency mosaic variants in some patients, enhancing the accuracy of TSC diagnosis.
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Context: Patients with congenital hyperinsulinism due to ABCC8 variants generally present severe hypoglycemia and those who do not respond to medical treatment typically undergo pancreatectomy. Few data exist on the natural history of non-pancreatectomized patients.

Objective: This work aims to describe the genetic characteristics and natural history in a cohort of non-pancreatectomized patients with congenital hyperinsulinism due to variants in the ABCC8 gene.

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TANGO2-related disease is an autosomal recessive multisystem disease associated with developmental delay and infancy-onset recurrent metabolic crises with early mortality. Several studies have reported dysfunction in endoplasmic reticulum-to-Golgi traffic and mitochondrial homoeostasis as the underlying pathophysiology. We report a 40-year-old woman affected by limb-girdle weakness and mild intellectual disability caused by the recurrent deletion of exons 3-9 in homozygosity in the TANGO2 gene.

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RRM2B encodes the p53-inducible small subunit (p53R2) of ribonucleotide reductase, a key protein for mitochondrial DNA (mtDNA) synthesis. Pathogenic variants in this gene result in familial mitochondrial disease in adults and children, secondary to a maintenance disorder of mtDNA. This study describes two patients, mother and son, with early-onset chronic progressive external ophthalmoplegia (PEO).

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Background: Consanguineous couples have an increased risk of severe diseases in offspring due to autosomal recessive disorders. Exome sequencing (ES) offers the possibility of extensive preconception carrier screening (PCS) in consanguineous couples who may be at risk of rare genetic disorders.

Methods: We retrospectively analysed ES data from 65 probands affected with rare genetic disorders born from consanguineous couples.

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  • Chronic progressive external ophthalmoplegia (CPEO) plus syndrome is linked to genetic mutations in the TOP3A gene.
  • Previously, this condition had only been documented in one patient, but a new study reports two adult siblings with the same genetic variant.
  • The siblings both have a specific mutation in the TOP3A gene (c.614A>G), leading to CPEO plus syndrome.
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Clinical exome sequencing has the potential to identify pathogenic variants unrelated to the purpose of the study (secondary findings, SFs). Data describing actual choices of SFs in participants in a clinical setting and factors influencing their decision are virtually non-existant in Europe. In this work, we report the acceptance rate of SFs, calculate their prevalence and study factors associated with the decision in a cohort of patients affected with a rare genetic disorder in a Spanish Hospital.

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Background/objectives: Exome sequencing may identify pathogenic variants unrelated with the purpose of the analysis. We investigated the frequency of secondary and incidental findings (SF/IF) in cancer susceptibility genes (CSG), their clinical actionability and the psychological impact in individuals with an SF/IF (cases) compared with individuals tested due to their cancer history (controls).

Methods: This study analysed 533 exomes ordered for non-cancer conditions.

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Methods to reconstruct the mitochondrial DNA (mtDNA) sequence using short-read sequencing come with an inherent bias due to amplification and mapping. They can fail to determine the phase of variants, to capture multiple deletions and to cover the mitochondrial genome evenly. Here we describe a method to target, multiplex and sequence at high coverage full-length human mitochondrial genomes as native single-molecules, utilizing the RNA-guided DNA endonuclease Cas9.

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that can rarely affect young individuals. Juvenile ALS (JALS) is defined for individuals with an onset of the disease before the age of 25. The contribution of genetics to ALS pathology is a field of growing interest.

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The quantification of mitochondrial respiratory chain (MRC) enzymatic activities is essential for diagnosis of a wide range of mitochondrial diseases, ranging from inherited defects to secondary dysfunctions. MRC lesion is frequently linked to extended cell damage through the generation of proton leak or oxidative stress, threatening organ viability and patient health. However, the intrinsic challenge of a methodological setup and the high variability in measuring MRC enzymatic activities represents a major obstacle for comparative analysis amongst institutions.

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  • * Over two years, researchers analyzed 62 children, finding genetic causes in 30 patients, including mitochondrial diseases and Aicardi-Goutières syndrome, through various sequencing techniques.
  • * The study identified three distinct clusters of lesions, and while mitochondrial biomarkers were not very effective, an interferon signature was found in Aicardi-Goutières syndrome cases, leading to the suggestion of using next-generation sequencing for early diagnosis based on these clusters.
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