Individuals carrying single mutated copies of Collagen 10 alpha-1, (COL10A1) suffer from Metaphyseal chondrodysplasia, Schmid type, (MCDS), involving mild to moderate short stature and skeletal deformities of the limbs. We describe individuals with two mutated copies of COL10A1, exhibiting extreme short stature and severe lower limb deformities. However, individuals with single mutated copies had below […]
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Their loss is our gain: regressive evolution in vertebrates provides genomic models for uncovering human disease loci
What can an armadillo tell us about blindness and an anteater about dental disorders? Many animals have evolved traits that are similar to human genetic diseases, although for these animals the traits are adaptive, not disease-causing. Intriguingly, when animals possess these disease-mimicking traits, they frequently have disabling mutations in the same genes underlying the human […]
Mutations in SCAPER cause autosomal recessive retinitis pigmentosa with intellectual disability
Retinitis pigmentosa (RP) is a hereditary eye disease marked by progressive degeneration of the retina – the part of the eye that is home to the photosensitive cells. RP can occur by itself or in combination with other impairments. The latter cases are known as syndromic RP. We identified mutations in a gene named SCAPER […]
Heterogeneous clinical spectrum of DNAJC12-deficient hyperphenylalaninemia: from attention deficit to severe dystonia and intellectual disability
Hyperphenylalaninemia is one of the most common inherited metabolic diseases diagnosed in the newborn screening and until now follow-up investigation included differential diagnosis of phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficiency. With the description of patients with biallelic variants in co-chaperone DNAJC12 (van Spronsen et al 2017), the paradigm of hyperphenylalaninemia needs reconsideration. DNAJC12-deficient patients may […]
A common SLC26A4-linked haplotype underlying non-syndromic hearing loss with enlargement of the vestibular aqueduct
Two mutated copies of the SLC26A4 gene are associated with Pendred syndrome, comprised of bilateral hearing loss with enlargement of the vestibular aqueduct (EVA) and thyroid goiter. Other EVA patients have a normal thyroid gland and only one mutated copy of SLC26A4. Our study identified the same combination, or haplotype, of noncoding sequence variants upstream […]
Increased Breast Cancer Risk in MSH2 Carriers from a Large Canadian Familial Cancer Registry
Lynch Syndrome is an inherited condition involving several well-characterized mutations; MLH1, MSH2, MSH6, and PMS2. Affected families are counselled on their increased risk of numerous malignant diagnoses including colorectal cancer and endometrial cancer, as well as central nervous system malignancies and several other gastrointestinal and genitourinary cancers. Management of Lynch Syndrome includes prevention and surveillance, […]
Segregation of mitochondrial DNA mutations in the human placenta: implication for prenatal diagnosis of mtDNA disorders
Mitochondrial cytopathies are genetic diseases, some of which result from mutations affecting part of the multiple DNA molecules located within mitochondria (mtDNA). Coexistence of mutant and wild-type mtDNA molecules is called “heteroplasmy” and defines a “mutant load”. Disease symptoms occur when the mutant load surpasses a tissue-specific threshold. Owing to the absence of therapy and […]
A germline deletion of 9p21.3 presenting as familial melanoma, astrocytoma and breast cancer: clinical and genetic counselling challenges
Very few families with 9p21.3 deletion have been described. These families are at risk of developing melanoma and nerve sheath tumors. We report a family with several members affected by melanoma, astrocytoma, neurofibromas, and breast cancer. They have a 9p21.3 deletion containing 9 genes. While mutations within individual genes are associated with distinct hereditary cancer […]
Identification of the first dominant mutation of LAMA5 gene causing a complex multisystem syndrome due to dysfunction of the extracellular matrix
Laminin alpha 5 gene (LAMA5) plays a master role in the extracellular matrix in all mammalian tissues; mice defective of LAMA5 do not overcome embryonic life. In this paper a previously unknown autosomal dominant clinico-pathological syndrome is described which segregates with the mutation c.9418G>A (p.V3140M) of LAMA5 in an informative Italian family. The results of […]
Assessing genome-wide copy number variation in the Han Chinese population
Copy number variation (CNV) is an important source of human genetic diversity, which contributes to Mendelian disorders as well as complex diseases. We conducted a genome-wide CNV discovery in 451 males of Han Chinese by using high-density comparative hybridization arrays. The CNVs we reported are in high quality and representative of Han Chinese from 28 […]