A Homozygous NDUFS6 Variant Associated with Neuropathy and Optic Atrophy.

Background: The NADH dehydrogenase [ubiquinone] iron-sulfur protein 6 (NDUFS6) gene encodes for an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Bi-allelic NDUFS6 variants have been linked with a severe disorder mostly reported as a lethal infantile mitochondrial disease (LMID) or Leigh syndrome (LS).

Objective: Here, we identified a homozygous variant (c.

Prospective evaluation of NGS-based sequencing in epilepsy patients: results of seven NASGE-associated diagnostic laboratories.

Background: Epilepsy is one of the most common and disabling neurological disorders. It is highly prevalent in children with neurodevelopmental delay and syndromic diseases. However, epilepsy can also be the only disease-determining symptom.

Impact of cfDNA Reference Materials on Clinical Performance of Liquid Biopsy NGS Assays.

Background: Liquid biopsy enables the non-invasive analysis of genetic tumor variants in circulating free DNA (cfDNA) in plasma. Accurate analytical validation of liquid biopsy NGS assays is required to detect variants with low variant allele frequencies (VAFs).

Methods: Six types of commercial cfDNA reference materials and 42 patient samples were analyzed using a duplex-sequencing-based liquid biopsy NGS assay.

[Human genetic diagnostics in hereditary eye diseases : What does the ophthalmologist need to know].

Hereditary eye disorders can affect all ocular structures and can be accompanied by structural malformations (e.g. coloboma) or functional disorders (e.

Highly sensitive liquid biopsy Duplex sequencing complements tissue biopsy to enhance detection of clinically relevant genetic variants.

Background: Liquid biopsy (LB) is a promising complement to tissue biopsy for detection of clinically relevant genetic variants in cancer and mosaic diseases. A combined workflow to enable parallel tissue and LB analysis is required to maximize diagnostic yield for patients.

Methods: We developed and validated a cost-efficient combined next-generation sequencing (NGS) workflow for both tissue and LB samples, and applied Duplex sequencing technology for highly accurate detection of low frequency variants in plasma.

Case Report: DPM1-CDG: Novel Variant with Severe Phenotype and Literature Review.

Congenital disorders of glycosylation (CDG) type I include variants in the gene leading to DPM1-CDG. The nine previously reported patients showed developmental delay, seizures, electroencephalography abnormalities and dysmorphic features with varying disease onset and severity. Clinical features of a new patient are described.

Long-term chemoprevention in patients with adenomatous polyposis coli: an observational study.

Prospective short-term studies on effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) point towards a decrease in the number and size of polyps. Effectiveness and safety in the prevention of progression in familial polyposis with NSAIDs in long-term use, which is the prerequisite for therapeutic evaluation in prospective studies, is unknown. The total absolute observation period of 54 patients under sulindac was 399 patient years with a mean of 7.

Variants in exons 5 and 6 of ACTB cause syndromic thrombocytopenia.

Germline mutations in the ubiquitously expressed ACTB, which encodes β-cytoplasmic actin (CYA), are almost exclusively associated with Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF). Here, we report six patients with previously undescribed heterozygous variants clustered in the 3'-coding region of ACTB. Patients present with clinical features distinct from BWCFF, including mild developmental disability, microcephaly, and thrombocytopenia with platelet anisotropy.

Recurrent de novo BICD2 mutation associated with arthrogryposis multiplex congenita and bilateral perisylvian polymicrogyria.

Autosomal dominantly inherited mutations of BICD2 are associated with congenital-onset spinal muscular atrophy characterised by lower limb predominance. A few cases have also showed upper motor neuron pathology, including presenting with features resembling hereditary spastic paraplegia. The age-of-onset for the published families is usually at birth but also included cases with childhood- and adult-onset disease.

A de novo 1q23.3-q24.2 deletion combined with a GORAB missense mutation causes a distinctive phenotype with cutis laxa.

Gerodermia osteodysplastica is a recessive segmental progeroid disorder mainly characterized by wrinkled skin, generalized connective tissue weakness, infantile onset osteoporosis and normal intelligence. Coding mutations in GORAB, localized on chromosome 1q24.2, are the cause of this disease.

ADAMTSL4-associated isolated ectopia lentis: Further patients, novel mutations and a detailed phenotype description.

ADAMTSL4 mutations seem to be the most common cause of isolated ectoplia lentis (EL) and thus are important concerning the differential diagnosis of connective tissue syndromes with EL as main feature. In this study, we describe an additional cohort of patients with apparently isolated EL. All underwent a detailed clinical exam with cardiac evaluation combined with ADAMTSL4 mutation analysis.

The phenotypic spectrum of duplication 5q35.2-q35.3 encompassing NSD1: is it really a reversed Sotos syndrome?

Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID). Microduplications of 5q35.2-q35.

A novel germline KIT mutation (p.L576P) in a family presenting with juvenile onset of multiple gastrointestinal stromal tumors, skin hyperpigmentations, and esophageal stenosis.

Familial gastrointestinal stromal tumor (GIST) syndrome is a rare autosomal dominant genetic disorder. We report on a kindred in which 3 family members carry a germline mutation (c.1727T>C, p.

Generalized epilepsy in two patients with 5p duplication.

Background: There are only few reports on patients with duplications of the short arm of chromosome 5, with little information about concomitant epilepsy.

Patients: We report on two patients with generalized epilepsies since age 2.5 years, in whom array comparative genomic hybridization revealed microduplications of different sizes in the short arm of chromosome 5.

Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset endometrial cancer.

Background: Hereditary Breast and Ovarian Cancer Syndrome (HBOCS) and Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome) are two tumor predisposition syndromes responsible for the majority of hereditary breast and colorectal cancers. Carriers of both germline mutations in breast cancer genes BRCA1 or BRCA2 and in mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2 are very rare.

Case Presentation: We identified germline mutations in BRCA1 and in MSH6 in a patient with increased risk for HBOC diagnosed with endometrial cancer at the age of 46 years.

Macrocerebellum: significance and pathogenic considerations.

Macrocerebellum is a rare finding characterized by an abnormally large cerebellum. Only few patients with a syndromal or isolated macrocerebellum have been reported so far. This article aims to categorize the magnetic resonance imaging (MRI) findings, quantitate the macrocerebellum by volumetric analysis, characterize the neurological and dysmorphic features and cognitive outcome, and report the results of genetic analyses in children with macrocerebellum.

A homozygous microdeletion within ADAMTSL4 in patients with isolated ectopia lentis: evidence of a founder mutation.

Purpose: The purpose of the study was to look for ADAMTSL4 mutations in a cohort of German patients with isolated ectopia lentis from nonconsanguineous families.

Methods: Mutation screening was performed by PCR amplification of the coding exons of ADAMTSL4 and subsequent sequencing.

Results: An identical homozygous deletion of 20 bp of coding sequence within exon 6 (NM_019032.