Diagnosis Of Genetic Diseases

WES can elucidate the cause of hereditary cardiac diseases such as: hypertrophic cardiomyopathy, dilated cardiomyopathy, non-dilated left ventricular cardiomyopathy, short QT syndrome, long QT syndrome, Brugada syndrome, arrhythmogenic heart disease, cardiac arrhythmias, but also familial hypercholesterolemia, hyperlipidemia and congenital heart defects.

Inherited connective tissue diseases can manifest differently and affect blood vessels and joints and are often difficult to distinguish phenotypically.

WES for connective tissue diseases can identify syndromes such as, Ehlers-Danlos, Marfan, Loeys-Dietz, Cutis laxa, hereditary aortic aneurysm etc.

WES for eye diseases can identify a wide range of single-gene diseases affecting pathologies of different regions of the eye. It includes hereditary retinal dystrophies such as: melanchromatic retinopathy, color blindness, rod and cone dystrophy, congenital Leber’s amaurosis, macular dystrophies, Stargardt’s disease, corneal dystrophies, optic atrophies, glaucoma, cataracts and syndromic forms of retinal dystrophies such as Usher, Bardet-Biedl, Joubert, Senior-Løken and Stickler syndromes, as well as syndromic albinism.

Identification of a disease causing variant in these disorders can clarify the diagnosis and is important for predicting the course of the disease and the risk in family members. In some cases, the finding also allows for personalised gene therapy.

WES for metabolic diseases covers a range of cases with symptoms originating from various organs/systems such as: lysosomal storage disorders, disorders of peroxisome biogenesis, urea cycle disorders/ hyperammonemias, glycine encephalopathies, cerebral creatine deficiency, disorders of intracellular cobalamin metabolism, isolated methylmalonic oxidation, congenital hyperinsulinism, juvenile diabetes, glycogen storage disease, molybdenum cofactor deficiency, cerebral folate deficiency, porphyria.

Mitochondrial diseases caused by genetic variations in nuclear genes are also covered.

Neurodevelopmental delay (NDD) and intellectual disability (ID) are neurodevelopmental disorders with a prevalence ranging from 3%-19% of children aged 2-9 years. There is great phenotypic heterogeneity among patients in terms of range and severity and they may occur alone or in combination with multiple congenital abnormalities, dysmorphic features, behavioural problems and additional neurological features such as epilepsy. More than 700 genes are associated with neurodevelopmental disorders, making it difficult to identify the causative gene, resulting in 10%-15% of patients remaining undiagnosed.

WES has contributed to the diagnosis in 30%-50% of patients with neurodevelopmental disorders.

WES for neurodegenerative diseases covers a wide range of neurodegenerative diseases such as: Alzheimer’s disease, Parkinson’s disease, paroxysmal movement disorders, intracerebral calcification, dystonia, frontotemporal dementia, motor neuron disorders, hereditary ataxia, dementia, congenital spastic paraplegia, leukodystrophy and leukoencephalopathy.

WES for epilepsy includes diseases such as: diopathic and congenital epilepsy, progressive myoclonic epilepsy, epileptic encephalopathy, DRAVET syndrome, familial temporal lobe epilepsy, neuronal waxy lipofuscinosis, migraines.

Genetic analysis for neuromuscular diseases includes genetic diseases of the muscle and muscle-activating nerve fibres, in which the muscle is indirectly affected.

WES for neuromuscular diseases covers a range of neuromuscular diseases such as: hereditary neuropathies with neuromuscular involvement, Emery-Dreifuss muscular dystrophy, other muscular dystrophies, congenital myasthenia, myotonia, metabolic myopathies, atrophy, periodic paralysis, Walker-Warburg syndrome.

WES for skeletal disorders includes a range of inherited diseases with skeletal contribution such as; skeletal malformations, osteogenesis imperfecta, limb malformations, subphosphatemic rickets, craniosynostosis, osteopetrosis and other skeletal disorders with increased bone density, genetic syndromes with skeletal malformations (s. Kabuki, s. Seckel, s. Rubistein-Taybi syndromes, etc), multiple exostoses and lysosomal diseases with skeletal involvement.

WES for skin diseases covers a range of inherited diseases with dermatological contribution such as: oculodermal albinism, hyperpigmentation diseases, ichthyosis, genetic disorders associated with epidermolysis, ectodermal dysplasia-tooth agenesis-and hypertrichosis, congenital dyskeratosis, photodermatosis, progeria and primary lipodystrophy syndromes, primary lymphedema, and neurocutaneous diseases such as neurofibromatosis type 1 and 2, Legius syndrome, tuberous sclerosis 1 and 2, schwannomatosis, Noonan syndrome, Leopard syndrome, Costello syndrome, cranio-facial-dermal syndrome.

WES concerns liver diseases with genetic aetiology. It includes diseases such as, haemochromatosis, α1-antitrypsin deficiency, Wilson’s disease, progressive familial intrahepatic cholestasis, lysosomal storage disorders involving the liver.

Diagnosis of the exact cause of each disease is essential for proper treatment.

WES in patients with kidney diseases contributes not only to targeted treatment but also provides indications for successful transplantation.
WES can identify a range of kidney diseases such as: polycystic kidney disease, nephropathy, focal segmental glomerulosclerosis, nephrotic syndrome, Alport syndrome and glomerular basement membrane disorders, renal tubular acidosis, hypophosphatemic rickets, pseudoaldosteronism, nephrogenic diabetes, hyperoxaluria, atypical haemolytic uraemic syndrome and differential diagnosis.