American journal of medical genetics. Part A
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Am. J. Med. Genet. A · Feb 2008
Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function.
Schnyder crystalline corneal dystrophy (SCCD) is a rare autosomal dominant disease characterized by progressive corneal opacification resulting from abnormal deposition of cholesterol and phospholipids. Recently, six different mutations on the UBIAD1 gene on chromosome 1p36 were found to result in SCCD. The purpose of this article is to further characterize the mutation spectrum of SCCD and identify structural and functional consequences for UBIAD1 protein activity. ⋯ The results suggest that N102S may be a mutation hot spot because the affected families were unrelated including Caucasian and Asian individuals. There was no genotype phenotype correlation except for the T175I mutation which demonstrated prominent diffuse corneal haze, typically without corneal crystals. Protein analysis revealed structural and functional implications of SCCD mutations which may affect UBIAD1 function, ligand binding and interaction with binding partners, like apo E.
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Am. J. Med. Genet. A · Aug 2007
Case ReportsAn association of Hutchinson-Gilford progeria and malignancy.
Mutations in the LMNA gene encoding lamins A/C are responsible for a variety of disorders, commonly referred to as "laminopathies," including the segmental premature aging syndrome Hutchinson-Gilford progeria. We describe in this report the rare association of osteosarcoma and slowly progressing progeria in an 11-year-old girl carrying a truncating heterozygous c.1868C > G (p. T623S) prelamin A mutation. These findings are discussed in light of recent data on the pathophysiological mechanisms underlying progeria and "physiological" aging in human, as well as previous data on other well-known segmental aging syndromes.
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Am. J. Med. Genet. A · Jul 2007
A case for genetics education: collaborating with speech-language pathologists and audiologists.
Because speech-language pathologists (SLPs) and audiologists (AUDs) are among the first referrals for parents of children exhibiting feeding, speech, language, hearing, and balance difficulties, it is important for SLP and AUD professionals to recognize genetic causes of and contributions to complex and Mendelian communication disorders. We review genetics in the curricula of speech-language pathology and audiology programs and obstacles to its integration throughout curricula. ⋯ The need to integrate genetics content into curricula and continuing education across disciplines is clear, as is the need for and benefit of multidisciplinary collaboration in patient care. The NCHPEG site for speech-language pathology and audiology begins to address those needs and may serve as a practical model for future multidisciplinary collaborations between genetics professionals and other health professions.
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Am. J. Med. Genet. A · Feb 2007
Case ReportsSkin changes in oculo-dento-digital dysplasia are correlated with C-terminal truncations of connexin 43.
Oculo-dento-digital dysplasia (ODDD, OMIM no.164210) is a pleiotropic disorder caused by mutations in the GJA1 gene that codes for the gap junction protein connexin 43. While the gene is highly expressed in skin, ODDD is usually not associated with skin symptoms. We recently described a family with ODDD and palmoplantar keratoderma. ⋯ We speculated, that truncation of the C-terminus may be uniquely associated with skin disease in ODDD. Here, we describe a patient with ODDD and palmar hyperkeratosis caused by a novel dinucleotide deletion that truncates most of the connexin 43 C-terminus. Thus, our findings support the notion that such mutations are associated with the occurrence of skin symptoms in ODDD and provide the first evidence for the existence of a genotype-phenotype correlation.
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Am. J. Med. Genet. A · Feb 2007
Case ReportsSevere hypertelorism, midface prominence, prominent/simple ears, severe myopia, borderline intelligence, and bone fragility in two brothers: new syndrome?
We report on two brothers, born to double first cousin Jordanian Arab parents, with a syndrome comprising severe hypertelorism with upslanted palpebral fissures, brachycephaly, abnormal ears, sloping shoulders, enamel hypoplasia, and osteopenia with repeated fractures. Both have severe myopia, mild to moderate sensori-neural hearing loss and borderline intelligence. ⋯ The father has mild hypertelorism but the family history is otherwise unremarkable. We think that this represents a previously unrecognized autosomal or X-linked recessive syndrome.