Publications by authors named "Alfonso Caro-Llopis"

Article Synopsis
  • Germline variants in the phosphatidylinositol glycan class A gene lead to MCAHS2, a syndrome marked by multiple congenital anomalies, seizures, and hypotonia, inherited in an X-linked recessive manner.
  • A case study presents a male infant with MCAHS2 due to a novel variant from his mother, who exhibited a non-skewed pattern of X-chromosome inactivation, which is uncommon in typical cases.
  • The study suggests using flow-cytometry tests to assess GPI-anchored protein expression, particularly CD16, in neutrophils of carrier mothers with random X-inactivation to better understand the pathogenic implications of gene variants affecting GPI-APs.
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  • Amino-terminal acetylation (NTA) is a crucial modification affecting approximately 80% of cytosolic proteins in humans, with NAA10 and NAA15 genes playing key roles in this process.
  • This study uncovers genetic variations in NAA10 and NAA15, analyzing 106 cases for NAA10 and 66 for NAA15, showing significant clinical and functional differences between individuals with these variants.
  • The resultant phenotypic spectrum includes various disabilities and health issues, such as intellectual disabilities, autism, and visual impairments, highlighting the broad impact of disturbances in the NTA pathway across multiple organ systems.
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Purpose: Biallelic PIGN variants have been described in Fryns syndrome, multiple congenital anomalies-hypotonia-seizure syndrome (MCAHS), and neurologic phenotypes. The full spectrum of clinical manifestations in relation to the genotypes is yet to be reported.

Methods: Genotype and phenotype data were collated and analyzed for 61 biallelic PIGN cases: 21 new and 40 previously published cases.

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Purpose: WNK3 kinase (PRKWNK3) has been implicated in the development and function of the brain via its regulation of the cation-chloride cotransporters, but the role of WNK3 in human development is unknown.

Method: We ascertained exome or genome sequences of individuals with rare familial or sporadic forms of intellectual disability (ID).

Results: We identified a total of 6 different maternally-inherited, hemizygous, 3 loss-of-function or 3 pathogenic missense variants (p.

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Background: Expand the knowledge about the clinical phenotypes associated with pathogenic or likely pathogenic variants in the gene.

Methods: The study was carried out in 15 patients with variants. The complete phenotype of the patients was evaluated.

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Dominant pathogenic variations in the gene are associated with several neuro developmental disorders with or without epilepsy, including Dravet syndrome (DS). Conversely, there are few published cases with homozygous or compound heterozygous variations in the gene. Here, we describe two siblings from a consanguineous pedigree with epilepsy phenotype compatible with genetic epilepsy with febrile seizures plus (GEFS+) associated with the homozygous likely pathogenic variant (NM_001165963.

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Article Synopsis
  • - The rise of assisted reproductive technologies has resulted in a significant number of births, with most children being healthy, but concerns about procedural safety persist.
  • - A study analyzed 486 children born between 2010 and 2019 with developmental issues and found a higher occurrence of harmful genetic variants in those conceived via in vitro fertilization with donor eggs compared to natural conception.
  • - No similar genetic issues were found in children conceived using their own eggs, prompting the need for further research to understand the causes of genetic changes in donor oocyte cases and the potential for prenatal genetic screening.
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Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder that causes movement and postural disabilities. Recent research studies focused on genetic diagnosis in patients with CP of unknown etiology. The present study was carried out in 20 families with one family member affected with idiopathic CP.

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Introduction: Schaaf-Yang syndrome (SYS) is caused by truncating point mutations of the paternal allele of , an imprinted gene located in the critical region of Prader-Willi syndrome (PWS). These patients present a phenotype with neurodevelopmental delay, hypotonia, joint contractures, and a particularly high prevalence of autism (up to 75% in affected individuals). The loss of function of is suggested to contribute to endocrine hypothalamic dysfunction in individuals with PWS.

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Schaaf-Yang syndrome (SYS) was recently identified as a genetic condition resembling Prader-Willi syndrome. It is caused by mutations on the paternal allele of the MAGEL2 gene, a gene that has been mapped in the Prader-Willi critical region. Here, we present an infant with SYS who sadly died because of the combination of hypotonia, sleep apnea, and obesity.

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De novo germline mutations in GNB1 have been associated with a neurodevelopmental phenotype. To date, 28 patients with variants classified as pathogenic have been reported. We add 18 patients with de novo mutations to this cohort, including a patient with mosaicism for a GNB1 mutation who presented with a milder phenotype.

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Whole-gene duplications and missense variants in the HUWE1 gene (NM_031407.6) have been reported in association with intellectual disability (ID). Increased gene dosage has been observed in males with non-syndromic mild to moderate ID with speech delay.

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We report on three nonrelated patients with intellectual disability and CNVs that give rise to three new chimeric genes. All the genes forming these fusion transcripts may have an important role in central nervous system development and/or in gene expression regulation, and therefore not only their deletion or duplication but also the resulting chimeric gene may contribute to the phenotype of the patients. Deletions and duplications are usually pathogenic when affecting dose-sensitive genes.

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Article Synopsis
  • - The study focused on diagnosing syndromic intellectual disability by sequencing a large panel of 1256 genes in 92 patients who had negative previous genetic analyses, aiming to identify mutations linked to the condition.
  • - A definitive diagnosis was achieved in 29 families, discovering mutations in 25 different genes, with KMT2D, KMT2A, and MED13L being the most frequently mutated, leading to a diagnostic yield of 39%.
  • - The research highlights the effectiveness of next-generation sequencing in identifying genetic variations, but also emphasizes the need for better clinical interpretation of these findings and further exploration of unknown genes associated with intellectual disability.
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Background: Mutations in the X-linked gene MED12 cause at least three different, but closely related, entities of syndromic intellectual disability. Recently, a new syndrome caused by MED13L deleterious variants has been described, which shows similar clinical manifestations including intellectual disability, hypotonia, and other congenital anomalies.

Methods: Genotyping of 1,256 genes related with neurodevelopment was performed by next-generation sequencing in three unrelated patients and their healthy parents.

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We describe an X-linked genetic syndrome associated with mutations in TAF1 and manifesting with global developmental delay, intellectual disability (ID), characteristic facial dysmorphology, generalized hypotonia, and variable neurologic features, all in male individuals. Simultaneous studies using diverse strategies led to the identification of nine families with overlapping clinical presentations and affected by de novo or maternally inherited single-nucleotide changes. Two additional families harboring large duplications involving TAF1 were also found to share phenotypic overlap with the probands harboring single-nucleotide changes, but they also demonstrated a severe neurodegeneration phenotype.

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