Publications by authors named "Manou Sommen"

In this study, we investigated the association of ACAN variants with otosclerosis, a frequent cause of hearing loss among young adults. We sequenced the coding, 5'-UTR and 3'-UTR regions of ACAN in 1497 unrelated otosclerosis cases and 1437 matched controls from six different subpopulations. The association between variants in ACAN and the disease risk was tested through single variant and gene-based association tests.

View Article and Find Full Text PDF

The involvement of genetic factors in the pathogenesis of KC has long been recognized but the identification of variants affecting the underlying protein functions has been challenging. In this study, we selected 34 candidate genes for KC based on previous whole-exome sequencing (WES) and the literature, and resequenced them in 745 KC patients and 810 ethnically matched controls from Belgium, France and Italy. Data analysis was performed using the single variant association test as well as gene-based mutation burden and variance components tests.

View Article and Find Full Text PDF

We investigated the interaction between osmotic stress and auxin signaling in leaf growth regulation. Therefore, we grew Arabidopsis thaliana seedlings on agar media supplemented with mannitol to impose osmotic stress and 1-naphthaleneacetic acid (NAA), a synthetic auxin. We performed kinematic analysis and flow-cytometry to quantify the effects on cell division and expansion in the first leaf pair, determined the effects on auxin homeostasis and response (DR5::β-glucuronidase), performed a next-generation sequencing transcriptome analysis and investigated the response of auxin-related mutants.

View Article and Find Full Text PDF

Otosclerosis is a common form of hearing loss (HL) due to abnormal remodeling of the otic capsule. The genetic causes of otosclerosis remain largely unidentified. Only mutations in a single gene, SERPINF1, were previously published in patients with familial otosclerosis.

View Article and Find Full Text PDF

Purpose: To characterize new molecular factors implicated in a hereditary congenital facial paresis (HCFP) family and otosclerosis.

Methods: We performed exome sequencing in a four-generation family presenting nonprogressive HCFP and mixed hearing loss (HL). MEPE was analyzed using either Sanger sequencing or molecular inversion probes combined with massive parallel sequencing in 89 otosclerosis families, 1604 unrelated affected subjects, and 1538 unscreened controls.

View Article and Find Full Text PDF

Objectives: The purpose of this study is to report the results of a comprehensive etiological work-up for congenitally deaf children including targeted next generation sequencing.

Study Design: Retrospective case review.

Setting: Tertiary referral center.

View Article and Find Full Text PDF

Inherited Palmoplantar Keratodermas are rare disorders of genodermatosis that are conventionally regarded as autosomal dominant in inheritance with extensive clinical and genetic heterogeneity. This is the first report of a unique autosomal recessive Inherited Palmoplantar keratoderma -sensorineural hearing loss syndrome which has not been reported before in 3 siblings of a large consanguineous family. The patients presented unique clinical features that were different from other known Inherited Palmoplantar Keratodermas -hearing loss syndromes.

View Article and Find Full Text PDF

Hearing loss (HL) is the most common birth defect in industrialized countries with far-reaching social, psychological and cognitive implications. It is an extremely heterogeneous disease, complicating molecular testing. The introduction of next-generation sequencing (NGS) has resulted in great progress in diagnostics allowing to study all known HL genes in a single assay.

View Article and Find Full Text PDF

Although there are nearly 100 different causative genes identified for nonsyndromic hearing loss (NSHL), Sanger sequencing-based DNA diagnostics usually only analyses three, namely, GJB2, SLC26A4, and OTOF. As this is seen as inadequate, there is a need for high-throughput diagnostic methods to detect disease-causing variations, including single-nucleotide variations (SNVs), insertions/deletions (Indels), and copy-number variations (CNVs). In this study, a targeted resequencing panel for hearing loss was developed including 79 genes for NSHL and selected forms of syndromic hearing loss.

View Article and Find Full Text PDF

Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. We ascertained eight families affected by HS and, by using a whole-exome sequencing approach, identified biallelic mutations in PEX1 or PEX6 in six of them. Loss-of-function mutations in both genes are known causes of a spectrum of autosomal-recessive peroxisome-biogenesis disorders (PBDs), including Zellweger syndrome.

View Article and Find Full Text PDF

Background/hypothesis: Otosclerosis is a frequent cause of hearing impairment characterized by abnormal resorption and deposition of bone in the human otic capsule. It is a disease of complex etiopathogenesis that is caused by both environmental and genetic factors. The goal of this study is to replicate association for genes that were previously reported to be associated with otosclerosis.

View Article and Find Full Text PDF

Implementing DNA diagnostics in clinical practice for extremely heterogeneous diseases such as hearing loss is challenging, especially when attempting to reach high sensitivity and specificity in a cost-effective fashion. Next generation sequencing has enabled the development of such a test, but the most commonly used genomic target enrichment methods such as hybridization-based capture suffer from restrictions. In this study, we have adopted a new flexible approach using microdroplet PCR-based technology for target enrichment, in combination with massive parallel sequencing to develop a DNA diagnostic test for autosomal recessive hereditary hearing loss.

View Article and Find Full Text PDF
Article Synopsis
  • CaBPs are a group of proteins that bind calcium ions and are found in the brain and sensory organs like the retina and cochlea; their full functions in calcium signaling are still being studied.
  • A specific mutation in the CABP2 gene (c.637+1G>T) was discovered in three Iranian families, likely contributing to moderate-to-severe hearing loss due to skipping of an exon that results in a shorter, dysfunctional protein.
  • This altered CABP2 shows impaired calcium binding and reduced ability to regulate calcium channels, indicating its role in causing hearing impairment related to calcium signaling issues in the inner ear.
View Article and Find Full Text PDF