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The localization and identification of the photoreceptor cell-specific nuclear gene NR2E3 as a novel disease locus and gene for 'autosomal dominant retinitis pigmentosa' (adRP) is described. A different pathogenetic mechanism is proposed for these distinct dominant and recessive phenotypes, which is attributed to the dual key role of NR2E3 in the regulation-specific genes during rod development and maintenance.

The clinical and molecular characterization of people presenting symptoms of the Loeys-Dietz syndrome was undertaken to distinguish them from the similar symptoms of vascular Ehlers-Danlos syndrome. Aggressive arterial aneurysms, such as thoracic aortic aneurysms and aortic dissection, are found to be caused by mutations in the genes encoding the transforming growth factor beta (TGF-beta) I or II, a distinguishing feature of the Loeys-Dietz syndrome.

Fluctuating, progressive autosomal dominant nonsyndromic hearing loss (ADNSHL) has been linked to a sixteenth gene, DFNA16, a gene that maps to chromosome 2q23-24.3. DFNA16 is unique and gives rise to the only form of ADNSHL with a phenotype involved in rapidly progressing and fluctuating hearing loss that seems to respond to steroid therapy. It may be possible to stabilize hearing through medical intervention after the biophysiology of DFNA16-related deafness is better understood. Several voltage-gated sodium-channel genes have been localized to the DFNA16 interval.

Hereditary hearing loss that begins early in life may be traced to a gene on chromosome 1p. Researchers studied a large Indonesian family with hereditary, progressive deafness. DNA samples were analyzed from 15 family members with hearing loss. A genetic-linkage analysis was performed to pinpoint the location of the gene for deafness. The gene was localized between D1S211 and D1S201 on chromosome 1p. Linkage analysis was then performed in American and Dutch families with hereditary hearing loss to determine if the same region on chromosome 1p was the location of the gene for deafness. In the American family, the gene was positioned on D1S255 on chromosome 1p. In the Dutch family, the gene for deafness was not located in the suspected region on chromosome 1p. Because the Indonesian and American families are of different ethnic groups, researchers suspect that the gene that causes deafness on chromosome 1p may be responsible for hereditary hearing loss in other families.

X-linked adrenoleukodystrophy comprises a group of inherited diseases, the most common types of which are childhood adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN). The former is characterized by normal development up to about 7 years, followed by swift mental and physical deterioration and death by 10 years of age. The average age of onset in AMN is 28 years, and patients (all male) experience partial paralysis of the legs and sensory, mental, and adrenal gland dysfunction. Half of the female carriers of the disease have similar deficits, generally occurring after 40 years of age. The primary cause of these diseases appears to be the deficiency of an enzyme that breaks down certain fats (very long-chain fatty acids), so that the fats accumulate in brain, adrenal gland, and other cells throughout the body. The ALD/AMN gene has not yet been isolated, but has been localized to a position on the X (female) chromosome called Xq28. Further localization of the gene by genetic analysis has been performed using tissues from 32 members of a family. Diagnosis of ALD or AMN was ascertained by laboratory tests for blood levels of certain fatty acids. Genetic analysis identified a carrier who was not found by the blood tests. ALD and AMN localized to the same area on chromosome X, suggesting that both diseases are due to a mutation in the same gene. The mutation segregated with linked genes coded b-5-a, where b and a are recessive genes for clotting factor VIII and DXS15 (function unknown), and 5 is the fifth of a group of 5 genes at DXS52 (function unknown). Other nonmutated genes or environmental factors may contribute to the medical differences between ALD and AMN. A large number of disorders have been mapped to Xq27 to Xq28. Notably, red/green color blindness is one such disease, and color vision defects are often associated with AMN/ALN, suggesting the mutations are close. Combination of genetic analysis with biochemical tests for fatty acids appears to provide the most effective methods for prenatal diagnosis for female carriers of AMN/ALD. (Consumer Summary produced by Reliance Medical Information, Inc.)