Loss of maternal chromosome 11 is a signature event in SDHAF2, SDHD, and VHL-related paragangliomas, but less significant in SDHB-related paragangliomas.

Germline mutations in the succinate dehydrogenase (SDHA, SDHB, SDHC, SDHD, SDHAF2) or Von Hippel-Lindau (VHL) genes cause hereditary paraganglioma/pheochromocytoma. While SDHB (1p36) and VHL (3p25) are associated with autosomal dominant disease, SDHD (11q23) and SDHAF2 (11q13) show a remarkable parent-of-origin effect whereby tumor formation is almost completely dependent on paternal transmission of the mutant allele. Loss of the entire maternal copy of chromosome 11 occurs frequently in SDHD-linked tumors, and has been suggested to be the basis for this typical inheritance pattern.

The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands.

Hearing impairment (HI) is genetically heterogeneous which hampers genetic counseling and molecular diagnosis. Testing of several single HI-related genes is laborious and expensive. In this study, we evaluate the diagnostic utility of whole-exome sequencing (WES) targeting a panel of HI-related genes.

A Comparison of Surgical Treatments for Superior Semicircular Canal Dehiscence: A Systematic Review.

Objective: We investigate the postoperative subjective and objective outcomes of different surgical treatments for superior semicircular canal dehiscence (SSCD): vestibular signs, auditory signs, vestibular evoked myogenic potential test, pure tone audiogram, speech audiogram, or video-nystagmography.

Data Sources: An electronic search performed in the PubMed, Cochrane Library, and EMBASE databases on 15th of September 2015. A systematic search was conducted.

Paediatric Cochlear Implantation in Patients with Waardenburg Syndrome.

Objective: To analyse the benefit of cochlear implantation in young deaf children with Waardenburg syndrome (WS) compared to a reference group of young deaf children without additional disabilities.

Method: A retrospective study was conducted on children with WS who underwent cochlear implantation at the age of 2 years or younger. The post-operative results for speech perception (phonetically balanced standard Dutch consonant-vocal-consonant word lists) and language comprehension (the Reynell Developmental Language Scales, RDLS), expressed as a language quotient (LQ), were compared between the WS group and the reference group by using multiple linear regression analysis.

Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2.

Linkage analysis combined with whole-exome sequencing in a large family with congenital and stable non-syndromic unilateral and asymmetric hearing loss (NS-UHL/AHL) revealed a heterozygous truncating mutation, c.286_303delinsT (p.Ser96Ter), in KITLG.

Inactivation of SDH and FH cause loss of 5hmC and increased H3K9me3 in paraganglioma/pheochromocytoma and smooth muscle tumors.

Succinate dehydrogenase (SDH) and fumarate hydratase (FH) are tricarboxylic acid (TCA) cycle enzymes and tumor suppressors. Loss-of-function mutations give rise to hereditary paragangliomas/pheochromocytomas and hereditary leiomyomatosis and renal cell carcinoma. Inactivation of SDH and FH results in an abnormal accumulation of their substrates succinate and fumarate, leading to inhibition of numerous α-ketoglutarate dependent dioxygenases, including histone demethylases and the ten-eleven-translocation (TET) family of 5-methylcytosine (5 mC) hydroxylases.

Gamma Knife radiosurgery for vestibular schwannomas: evaluation of tumor control and its predictors in a large patient cohort in The Netherlands.

OBJECT The authors of this study sought to assess tumor control and complication rates in a large cohort of patients who underwent Gamma Knife radiosurgery (GKRS) for vestibular schwannoma (VS) and to identify predictors of tumor control. METHODS The records of 420 patients treated with GKRS for VS with a median marginal dose of 11 Gy were retrospectively analyzed. Patients with neurofibromatosis Type 2 or who had undergone treatment for VS previously were excluded.

Audiometric Characteristics of a Dutch DFNA10 Family With Mid-Frequency Hearing Impairment.

Objectives: Mutations in EYA4 can cause nonsyndromic autosomal dominant sensorineural hearing impairment (DFNA10) or a syndromic variant with hearing impairment and dilated cardiomyopathy. A mutation in EYA4 was found in a Dutch family, causing DFNA10. This study is focused on characterizing the hearing impairment in this family.

Nonmuscle Myosin Heavy Chain IIA Mutation Predicts Severity and Progression of Sensorineural Hearing Loss in Patients With MYH9-Related Disease.

Objectives: MYH9-related disease (MYH9-RD) is an autosomal- dominant disorder deriving from mutations in MYH9, the gene for the nonmuscle myosin heavy chain (NMMHC)-IIA. MYH9-RD has a complex phenotype including congenital features, such as thrombocytopenia, and noncongenital manifestations, namely sensorineural hearing loss (SNHL), nephropathy, cataract, and liver abnormalities. The disease is caused by a limited number of mutations affecting different regions of the NMMHC-IIA protein.

Mutations in DVL1 cause an osteosclerotic form of Robinow syndrome.

Robinow syndrome (RS) is a phenotypically and genetically heterogeneous condition that can be caused by mutations in genes encoding components of the non-canonical Wnt signaling pathway. In contrast, germline mutations that act to increase canonical Wnt signaling lead to distinctive osteosclerotic phenotypes. Here, we identified de novo frameshift mutations in DVL1, a mediator of both canonical and non-canonical Wnt signaling, as the cause of RS-OS, an RS subtype involving osteosclerosis, in three unrelated individuals.

Nonsyndromic hearing loss caused by USH1G mutations: widening the USH1G disease spectrum.

Objective: Currently, six genes are known to be associated with Usher syndrome type I, and mutations in most of these genes can also cause nonsyndromic hearing loss. The one exception is USH1G, which is currently only known to be involved in Usher syndrome type I and atypical Usher syndrome.

Design: A Dutch family with autosomal recessively inherited hearing loss was examined.

Karyotype-specific ear and hearing problems in young adults with Turner syndrome and the effect of oxandrolone treatment.

Objective: To evaluate karyotype-specific ear and hearing problems in young-adult patients with Turner syndrome (TS) and assess the effects of previous treatment with oxandrolone (Ox).

Study Design: Double-blind follow-up study.

Setting: University hospital.

Intrafamilial variable hearing loss in TRPV4 induced spinal muscular atrophy.

Objective: Mutations in the transient receptor potential vanilloid 4 gene (TRPV4) can induce a great diversity of neuropathies. Together with these neuropathies, hearing loss can occur. This study is focused on providing an audiometric phenotype description of a Dutch family with spinal muscular atrophy caused by a mutation in TRPV4.

Similar phenotypes caused by mutations in OTOG and OTOGL.

Objectives: Recently, OTOG and OTOGL were identified as human deafness genes. Currently, only four families are known to have autosomal recessive hearing loss based on mutations in these genes. Because the two genes code for proteins (otogelin and otogelin-like) that are strikingly similar in structure and localization in the inner ear, this study is focused on characterizing and comparing the hearing loss caused by mutations in these genes.

Genetics of hereditary head and neck paragangliomas.

Background: The purpose of this study was to give an overview on hereditary syndromes associated with head and neck paragangliomas (HNPGs).

Methods: Our methods were the review and discussion of the pertinent literature.

Results: About one third of all patients with HNPGs are carriers of germline mutations.

Genotype-specific abnormalities in mitochondrial function associate with distinct profiles of energy metabolism and catecholamine content in pheochromocytoma and paraganglioma.

Purpose: Pheochromocytomas and paragangliomas (PGL) are neuroendocrine tumors of sympathetic and parasympathetic paraganglia. This study investigated the relationships between genotype-specific differences in mitochondrial function and catecholamine content in PGL tumors.

Experimental Design: Respiratory chain enzyme assays and (1)H-nuclear magnetic resonance (NMR) spectroscopy at 500 MHz were conducted on homogenates of 35 sporadic PGLs and 59 PGLs from patients with hereditary mutations in succinate dehydrogenase subunits B and D (SDHB, SDHD), succinate dehydrogenase assembly factor 2, von Hippel-Lindau (VHL), rearranged during transfection (RET), neurofibromatosis type 1 (NF1), and myc-associated factor X.

A new bone-anchored hearing implant: short-term retrospective data on implant survival and subjective benefit.

This report provides the first short-term follow-up data on the Ponto bone-anchored hearing implant from our tertiary referral centre. Thirty-one consecutive patients with a mean age of 51 years who received the implant between October 2010 and December 2011 were included retrospectively in this study. Implant loss, skin reactions around the implant (according to Holgers' grading system), revision surgery, and abutment replacements were retrospectively gathered from the patients' files as objective outcome measures.

Mutations of the gene encoding otogelin are a cause of autosomal-recessive nonsyndromic moderate hearing impairment.

Already 40 genes have been identified for autosomal-recessive nonsyndromic hearing impairment (arNSHI); however, many more genes are still to be identified. In a Dutch family segregating arNSHI, homozygosity mapping revealed a 2.4 Mb homozygous region on chromosome 11 in p15.

Congenital ossicular chain anomalies associated with a mobile stapes footplate: surgical results for 23 ears.

Objectives: We describe the audiometric results following surgery in a consecutive series of patients with a congenital ossicular middle ear disorder that was associated with a mobile stapes footplate.

Methods: We performed a retrospective analysis of patient charts from a tertiary referral center. A total of 23 patients (23 ears) underwent exploratory tympanotomy and ossicular reconstruction between 1986 and 2001.

Disruption of teashirt zinc finger homeobox 1 is associated with congenital aural atresia in humans.

Congenital aural atresia (CAA) can occur as an isolated congenital malformation or in the context of a number of monogenic and chromosomal syndromes. CAA is frequently seen in individuals with an 18q deletion, which is characterized by intellectual disability, reduced white-matter myelination, foot deformities, and distinctive facial features. Previous work has indicated that a critical region for CAA is located in 18q22.

Congenital stapes ankylosis associated with another ossicular chain anomaly: surgical results in 30 ears.

Objective: To describe the audiometric results after stapes surgery in a consecutive series of patients with stapes footplate ankylosis combined with another ossicular middle ear anomaly.

Study Design: A retrospective analysis of charts collected between 1986 and 2001.

Setting: A tertiary referral center.

Genotype-phenotype correlation in DFNB8/10 families with TMPRSS3 mutations.

In the present study, genotype-phenotype correlations in eight Dutch DFNB8/10 families with compound heterozygous mutations in TMPRSS3 were addressed. We compared the phenotypes of the families by focusing on the mutation data. The compound heterozygous variants in the TMPRSS3 gene in the present families included one novel variant, p.