Pulmonary arterial hypertension (PAH) is a rare disease in which high blood pressure in vessels of the lung leads to heart failure and premature death. PAH is caused by various genetic and environmental factors, including recently identified autosomal dominant ATP13A3 variants causing adult-onset PAH. We report three families with a novel, autosomal recessive form of […]
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Expanding the phenotype of SPARC-related Osteogenesis Imperfecta: Clinical findings in two patients with pathogenic variants in SPARC and literature review
In this manuscript, we describe two individuals with a very rare form of osteogenesis imperfecta (OI, also known as brittle bone disease) caused due to faults within SPARC gene. There are only a handful of patients described in the literature with this OI type and all these patients have significant fractures, curvature of spine and […]
Biallelic GINS2 variant p.(Arg114Leu) causes Meier-Gorlin syndrome with craniosynostosis
We describe the first patient with a homozygous disease-causing missense variant in GINS2, a gene that encodes for a component of the DNA replication machinery. Our patient presented with craniosynostosis and fulfilled the clinical diagnosis of Meier-Gorlin syndrome (MGORS), including prenatal and postnatal growth delay, hypoplastic patellar, and typical craniofacial dysmorphisms, such as microtia. The […]
ARF1 haploinsufficiency causes periventricular nodular heterotopia with variable clinical expressivity
We report the first inherited ARF1variant in a girl with intellectual disability and periventricular nodular heterotopia, and in her father with previously undiagnosed single nodular heterotopia and mild clinical expression. Additionally, our patients presente some features suggestive for hypohidrotic ectodermal dysplasia. The clinical features of our patients showed similarities to those of three previously reported […]
Homozygous mutations in CCDC34 cause male infertility with oligoasthenoteratozoospermia in humans and mice
Oligoasthenoteratozoospermia characterized by multiple morphological abnormalities of the flagella (MMAF) has been a major reproductive disorder with a highly genetically heterogeneous. Novel MMAF-associated genes remain to be identified in genetically unexplained MMAF cases. In this study, we identified homozygous deleterious CCDC34 variants that induce MMAF-associated oligoasthenoteratozoospermia in humans and mice. Also, treatment prognosis of intracytoplasmic […]
Diagnostic Yield of Chromosomal Microarray and Trio Whole-Exome Sequencing in Cryptogenic Cerebral Palsy
Cerebral palsy (CP) is a permanent movement disorder caused by non-progressive abnormalities of the developing brain, occuring approximately one in 500 live births. In most, CP is associated with prematurity and asphyxia, but in about a third of patients there is no apparent cause. The goal of this project was to evaluate the diagnostic yields […]
Men with FMR1 premutation alleles of less than 71 CGG repeats have low risk of being affected with fragile X-associated tremor/ataxia syndrome (FXTAS)
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative condition, predominantly affecting males with a Fragile X premutation (CGG expansion in the FMR1 gene of 55-199 repeats). Current penetrance estimates are based on data from premutation carriers with larger than average CGG repeat size (>70) and suggest up to 45% of males will develop FXTAS […]
Delineating the genotypic and phenotypic spectrum of HECW2-related neurodevelopmental disorders
In this study, we expand and characterize the phenotypic spectrum and molecular landscape of HECW2-related neurodevelopmental disorders. Clinical characterization suggests complete penetrance for hypotonia with or without spasticity, developmental delay/intellectual disability and developmental language disorder. We also report that all pathogenic variants are missense and mainly clustered in and near the HECT domain of the […]
O’Donnell-Luria-Rodan syndrome: description of a second multinational cohort and refinement of the phenotypic spectrum
The O’Donnell-Luria-Rodan syndrome (ODLURO) is a disorder primarily affecting cognitive development and behavior. Patients often show delayed development, mild to moderate intellectual disability, a large head circumference and autism spectrum disorder. After it was first described in 2019, we now report the second systematic case series of 18 patients with ODLURO, leading to a better […]
Hypermobile Ehlers-Danlos syndrome (hEDS) phenotype in fragile X premutation carriers: case series
Although hypermobile Ehlers-Danlos syndrome (hEDS) is the most common type of EDS, its genetic etiology is unclear. This study presents 5 cases who had both a hEDS phenotype and FMR1 premutation. In premutation carriers, a possible connection between both conditions could be explained by a depletion of fragile X mental retardation protein (FMRP), a major […]