Healthy dental enamel is the hardest and most highly mineralized human tissue. Though acellular, nonvital, and without capacity for turnover or repair, it can nevertheless last a lifetime. Amelogenesis imperfecta (AI) is a collective term for failure of normal enamel development, covering diverse clinical phenotypes that typically show Mendelian inheritance patterns. One subset, known as hypoma...

PURPOSE To investigate the genetic basis of autosomal recessive congenital cataracts in a consanguineous Pakistani family. METHODS All affected individuals underwent a detailed ophthalmological and clinical examination. Blood samples were collected and genomic DNAs were extracted. A genome-wide scan was performed with polymorphic microsatellite markers. Logarithm of odds (LOD) scores were cal...

Clinical anophthalmia is a rare inherited disease of the eye and phenotype refers to the absence of ocular tissue in the orbit of eye. Patients may have unilateral or bilateral anophthalmia, and generally have short palpebral fissures and small orbits. Anophthalmia may be isolated or associated with a broader syndrome and may have genetic or environmental causes. However, genetic cause has been...

By using homozygosity mapping in a consanguineous Pakistani family, we detected linkage of nonsyndromic hearing loss to a 7.6 Mb region on chromosome 3q13.31-q21.1 within the previously reported DFNB42 locus. Subsequent candidate gene sequencing identified a homozygous nonsense mutation (c.1135G>T [p.Glu379X]) in ILDR1 as the cause of hearing impairment. By analyzing additional consanguineous f...

Causes of autosomal-recessive intellectual disability (ID) have, until very recently, been under researched because of the high degree of genetic heterogeneity. However, now that genome-wide approaches can be applied to single multiplex consanguineous families, the identification of genes harboring disease-causing mutations by autozygosity mapping is expanding rapidly. Here, we have mapped a di...

PURPOSE To further explore the spectrum of mutations in the Visual System Homeobox 2 (VSX2/CHX10) gene previously found to be associated with autosomal recessive microphthalmia. METHODS We screened 95 probands with syndromic or isolated developmental ocular conditions (including 55 with anophthalmia/microphthalmia) for mutations in VSX2. RESULTS Homozygous mutations in VSX2 were identified ...

Women harboring pathogenic germline mutations in the BRCA1 and BRCA2 genes have high lifetime risks of developing breast and ovarian cancer (1). Therefore, it is clinically relevant to identify individuals harboring BRCA1/2 mutations to optimize cancer risk management (2). Initially the genetic risk is assessed based on a comprehensive personal and family history of cancer. Genetic testing is t...

OBJECTIVES The aim of this paper is to describe the current knowledge about inherited diseases in UK children of Pakistani origin, who now number over 300,000, and to investigate disease associations with parental consanguinity. METHODS Published data on the overall prevalence of inherited diseases were reviewed in conjunction with published and unpublished information from the city of Bradfo...

Abstract Background Hearing loss/deafness is a common otological disorder found in the Pakistani population due to high prevalence of consanguineous unions, but full range genetic causes still unknown. Methods A large kindred with hearing loss was studied. Whole-exome sequencing and Sanger were performed search for candidate gene underlying disease phenotype. minigene assay reverse transcriptio...