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 […]
The focal facial dermal dysplasias: phenotypic spectrum and molecular genetic heterogeneity
Focal Facial Dermal Dysplasias (FFDDs) are four developmental genetic disorders with similar bilateral “scar-like” facial lesions at birth and are classified by the lesion location: bitemporal for the FFDD subtypes 1-3 and peri-auricular for FFDD subtype 4. This review summarizes the clinical features of the subtypes and the genetic defects underlying FFDD3 and FFDD4, while […]
Missense mutations in the WD40 domain of AHI1 cause non-syndromic retinitis pigmentosa
Pathogenic variants (mutations) in the Abelson helper integration site 1 (AHI1) gene are known to be associated with Joubert syndrome, a developmental disorder causing visual, cognitive and motor deficits. In this study, we show that some pathogenic variants in the AHI1 gene can cause visual impairment, without other symptoms or signs suggestive of Joubert syndrome. […]
First evidence of genotype-phenotype correlations in Gorlin syndrome
Gorlin syndrome (GS) is a genetic disease that causes affected people to develop skin tumours and puts them at risk of other tumours as well as other abnormal features of skin and bone. Most cases of GS are caused by gene changes in the PTCH1 gene, while fewer cases are caused by changes in the […]
Genetic causes of optic nerve hypoplasia
Optic nerve hypoplasia is characterized by the underdevelopment of the optic nerves, which carry the visual information from the retina to the brain. Optic nerve hypoplasia represents the most common congenital optic nerve anomaly and a leading cause of blindness in the United States. This review highlights the growing number of genes that have been […]
The BRCA1 R1699Q intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
Mutations in BRCA1 confer high life-time risks for breast cancer (BC): 68% and ovarian cancer (OC): 39%. Our paper describes the cancer risks associated with the missense mutation BRCA1*R1699Q in a large group of families ascertained internationally. Results show that the risks associated with this mutation, BC 20% and OC 6%, are lower than for the average BRCA1 mutations. Based on these […]
Female-to-male sex reversal associated with unique Xp21.2 deletion disrupting genomic regulatory architecture of the dosage-sensitive sex reversal region
During the early stages of embryo growth, the SRY gene located on the Y chromosome triggers male sexual development. Typically, embryos with two X chromosomes develop into females. We report a child with two X chromosomes who had male appearing genitalia (female-to-male sex reversal) due to a deletion of a small X chromosome segment controlling […]
Missense mutations in the WD40 domain of AHI1 cause non-syndromic retinitis pigmentosa
Pathogenic variants (mutations) in the Abelson helper integration site 1 (AHI1) gene are known to be associated with Joubert syndrome, a developmental disorder causing visual, cognitive and motor deficits. In this study, we show that some pathogenic variants in the AHI1 gene can cause visual impairment, without other symptoms or signs suggestive of Joubert syndrome. […]