Mutational Spectrum, Ocular and Olfactory Phenotypes of -Related RP-Olfactory Dysfunction Syndrome in a Multiethnic Cohort.

gene mutations are a well-known cause of autosomal recessive retinitis pigmentosa (RP), which was recently associated with olfactory dysfunction. The purpose of this study was to report the molecular spectrum and the ocular and olfactory phenotypes of a multiethnic cohort with -associated RP. A cross-sectional case series was conducted at two ophthalmic genetics referral centers.

Audiological Outcomes and Associated Factors after Pediatric Cochlear Reimplantation.

Cochlear implants are the most common and successful sensory neuroprosthetic devices. However, reimplantation can be required for medical reasons, device failure, or technological upgrading. Resolving the problem driving the intervention and offering stable or better audiological results are the main challenges.

Identification of the First Single Exon 8 Structural Variants Associated with Autosomal Dominant Hearing Loss.

, also known as , is a gene implicated in autosomal dominant nonsyndromic hearing loss (ADNSHL), affecting, at first, the high frequencies with a subsequent progression over all frequencies. To date, all the pathogenic variants associated with deafness lead to skipping of exon 8. In two families with apparent ADNSHL, massively parallel sequencing (MPS) integrating a coverage-based method for detection of copy number variations (CNVs) was applied, and it identified the first two causal structural variants affecting exon 8.

When Familial Hearing Loss Means Genetic Heterogeneity: A Model Case Report.

We describe a family with both hearing loss (HL) and thrombocytopenia, caused by pathogenic variants in three genes. The proband was a child with neonatal thrombocytopenia, childhood-onset HL, hyper-laxity and severe myopia. The child's mother (and some of her relatives) presented with moderate thrombocytopenia and adulthood-onset HL.

Pregnancy in MNGIE: a clinical and metabolic honeymoon.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an inherited disease caused by a deficiency in thymidine phosphorylase and characterized by elevated systemic deoxyribonucleotides and gastrointestinal (GI) and neurological manifestations. We report the clinical and biochemical manifestations that were evaluated in a single patient before, during, and after pregnancy, over a period of 7 years. GI symptoms significantly improved, and plasma deoxyribonucleotide concentrations decreased during pregnancy.

Hemangiol in infantile haemangioma: A paediatric post-marketing surveillance drug study.

Aim: Infantile haemangioma (IH) is the most common benign tumour in children. Since 2014, propranolol has become the first-choice therapy and currently Hemangiol is the only approved drug for complicated haemangioma. This post-marketing study reports the use of Hemangiol for IH in paediatric practice.

A 4.6 Mb Inversion Leading to - and - Fusion Transcripts as a New Pathogenic Mechanism Implicated in Usher Syndrome Type 1.

Usher type 1 syndrome is a rare autosomal recessive disorder involving congenital severe-to-profound hearing loss, development of vision impairment in the first decade, and severe balance difficulties. The gene, one of the five genes implicated in this disease, is involved in 8-20% of cases. In this study, we aimed to identify and characterize the two causal variants in a French patient with typical Usher syndrome clinical features.

SLC12A2 variants cause a neurodevelopmental disorder or cochleovestibular defect.

The SLC12 gene family consists of SLC12A1-SLC12A9, encoding electroneutral cation-coupled chloride co-transporters. SCL12A2 has been shown to play a role in corticogenesis and therefore represents a strong candidate neurodevelopmental disorder gene. Through trio exome sequencing we identified de novo mutations in SLC12A2 in six children with neurodevelopmental disorders.

POLR1B and neural crest cell anomalies in Treacher Collins syndrome type 4.

Purpose: Treacher Collins syndrome (TCS) is a rare autosomal dominant mandibulofacial dysostosis, with a prevalence of 0.2-1/10,000. Features include bilateral and symmetrical malar and mandibular hypoplasia and facial abnormalities due to abnormal neural crest cell (NCC) migration and differentiation.

Mutations in PLS1, encoding fimbrin, cause autosomal dominant nonsyndromic hearing loss.

Nonsyndromic hearing loss (NSHL), a common sensory disorder, is characterized by high clinical and genetic heterogeneity (i.e., approximately 115 genes and 170 loci so far identified).

WFS1 in Optic Neuropathies: Mutation Findings in Nonsyndromic Optic Atrophy and Assessment of Clinical Severity.

Purpose: To search for WFS1 mutations in patients with optic atrophy (OA) and assess visual impairment.

Design: Retrospective molecular genetic and clinical study.

Participants: Patients with OA followed at a national referral center specialized in genetic sensory diseases.

Whole USH2A Gene Sequencing Identifies Several New Deep Intronic Mutations.

Deep intronic mutations leading to pseudoexon (PE) insertions are underestimated and most of these splicing alterations have been identified by transcript analysis, for instance, the first deep intronic mutation in USH2A, the gene most frequently involved in Usher syndrome type II (USH2). Unfortunately, analyzing USH2A transcripts is challenging and for 1.8%-19% of USH2 individuals carrying a single USH2A recessive mutation, a second mutation is yet to be identified.

Neonatal respiratory distress syndrome revealing a cervical bronchogenic cyst: a case report.

Background: Bronchogenic cyst is a congenital malformation, rarely located in the cervical region and almost never involved in a neonate with acute respiratory distress in the delivery room.

Case Presentation: A female newborn with respiratory distress syndrome caused by a large left cervical mass. Intubation was difficult due to tracheal deviation.

Treacher Collins syndrome: a clinical and molecular study based on a large series of patients.

Purpose: Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C.

Neuroradiological findings expand the phenotype of OPA1-related mitochondrial dysfunction.

Objective: OPA1 mutations are responsible for more than half of autosomal dominant optic atrophy (ADOA), a blinding disease affecting the retinal ganglion neurons. In most patients the clinical presentation is restricted to the optic nerve degeneration, albeit in 20% of them, additional neuro-sensorial symptoms might be associated to the loss of vision, as frequently encountered in mitochondrial diseases. This study describes clinical and neuroradiological features of OPA1 patients.

Refining the audiological assessment in children using narrow-band CE-Chirp-evoked auditory steady state responses.

Objective: To demonstrate the feasibility and reliability of simultaneous binaural recording of auditory steady-state responses (ASSR) in young children using narrow-band CE-Chirps as stimuli.

Design: Prospective cohort study comparing ASSR thresholds to four frequency stimuli (0.5, 1, 2, and 4 kHz), with click-evoked auditory brainstem responses (ABR) and behavioral response audiometry.

Enrichment of LOVD-USHbases with 152 USH2A genotypes defines an extensive mutational spectrum and highlights missense hotspots.

Alterations of USH2A, encoding usherin, are responsible for more than 70% of cases of Usher syndrome type II (USH2), a recessive disorder that combines moderate to severe hearing loss and retinal degeneration. The longest USH2A transcript encodes usherin isoform b, a 5,202-amino-acid transmembrane protein with an exceptionally large extracellular domain consisting notably of a Laminin N-terminal domain and numerous Laminin EGF-like (LE) and Fibronectin type III (FN3) repeats. Mutations of USH2A are scattered throughout the gene and mostly private.

Large deletions encompassing the TCOF1 and CAMK2A genes are responsible for Treacher Collins syndrome with intellectual disability.

Mandibulofacial dysostosis is part of a clinically and genetically heterogeneous group of disorders of craniofacial development, which lead to malar and mandibular hypoplasia. Treacher Collins syndrome is the major cause of mandibulofacial dysostosis and is due to mutations in the TCOF1 gene. Usually patients with Treacher Collins syndrome do not present with intellectual disability.

Relative frequencies of inherited retinal dystrophies and optic neuropathies in Southern France: assessment of 21-year data management.

Purpose: Inherited retinal dystrophies (IRDs) and inherited optic neuropathies (IONs) are rare diseases defined by specific clinical and molecular features. The relative prevalence of these conditions was determined in Southern France.

Methods: Patients recruited from a specialized outpatient clinic over a 21-year period underwent extensive clinical investigations and 107 genes were screened by polymerase chain reaction/sequencing.

Variability in nitrogen content of submerged aquatic vegetation: utility as an indicator of N dynamics within and among lakes.

Submerged aquatic vegetation (SAV) may serve as an integrative proxy of spatial and temporal nitrogen (N) availability in aquatic ecosystems as plants are physiologically capable of storing variable amounts of N. However, it is important to understand whether plant species behave similarly or differently within and among systems. We sampled different SAV species along a nutrient gradient at multiple sites within several lakes to determine variability in C:N ratios and % N content among species, among plants of the same species at a single site, among sites and among lakes.

Non-USH2A mutations in USH2 patients.

We have systematically analyzed the two known minor genes involved in Usher syndrome type 2, DFNB31 and GPR98, for mutations in a cohort of 31 patients not linked to USH2A. PDZD7, an Usher syndrome type 2 (USH2) related gene, was analyzed when indicated. We found that mutations in GPR98 contribute significantly to USH2.

Usher syndrome type 2 caused by activation of an USH2A pseudoexon: implications for diagnosis and therapy.

USH2A sequencing in three affected members of a large family, referred for the recessive USH2 syndrome, identified a single pathogenic alteration in one of them and a different mutation in the two affected nieces. As the patients carried a common USH2A haplotype, they likely shared a mutation not found by standard sequencing techniques. Analysis of RNA from nasal cells in one affected individual identified an additional pseudoexon (PE) resulting from a deep intronic mutation.