A splice-site mutation affecting the paired box of PAX3 in a three generation family with Waardenburg syndrome type I (WS1)

Attaie, Ali; Kim, Eugene; Wilcox, Edward R.; Lalwani, Anil K.

doi:10.1006/mcpr.1997.0101

Cited by 8 publications

(9 citation statements)

References 11 publications

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“…It has been estimated that up to 15% of all diseasecausing point mutations result in defective splicing [Krawczak et al, 1992]. Although deafness-causing splice site mutations have been identified, only 10 of those reported affect the 3 0 acceptor splice site, making defects in this element of the splicing mechanism rare [Attaie et al, 1997;Coucke et al, 1999;Verpy et al, 2000;Yasunaga et al, 2000;Hertz et al, 2001;Scott et al, 2001;Maubaret et al, 2005]. Of the 10 reported mutations, only one was shown to alter splicing by introduction of a cryptic site distinct from the normal 3 0 splice site [Scott et al, 2001].…”

Section: Discussionmentioning

confidence: 99%

A novel splice site mutation in EYA4 causes DFNA10 hearing loss

Hildebrand

Coman

Yang

et al. 2007

American J of Med Genetics Pt A

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Nonsyndromic autosomal dominant sensorineural hearing loss (SNHL) at the DFNA10 locus was described in two families in 2001. Causative mutations that affect the EyaHR domain of the 'Eyes absent 4' (EYA4) protein were identified. We report on the clinical and genetic analyses of an Australian family with nonsyndromic SNHL. Screening of the EYA4 gene showed the novel polypyrimidine tract variation ca. 1,282-12T > A that introduces a new 3' splice acceptor site. This is the first report of a point mutation in EYA4 that is hypothesized to lead to aberrant pre-mRNA splicing and human disease. The DFNA10 family described is only the fourth to be identified. One individual presented with apparently the same phenotype as other affected members of the family. However, genotyping illustrated that he did not share the DFNA10 disease haplotype. Detailed clinical investigation showed differences in the onset and severity of his hearing loss and thus he is presumed to represent a phenocopy, perhaps resulting from long-term exposure to loud noise.

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Section: Discussionmentioning

confidence: 99%

A novel splice site mutation in EYA4 causes DFNA10 hearing loss

Hildebrand

Coman

Yang

et al. 2007

American J of Med Genetics Pt A

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“…Defects in the PAX3 gene, a transcription factor expressed during embryonic development, have been shown to cause WS types I and III in several families. In contrast, mutations in PAX3 do not cause WS type II, and linkage of the disease to other chromosomal regions has been demonstrated 7,17 . While mutations in the gene PAX3 seem to be responsible for most WS type I, it is still not clear what accounts for the reduced penetrance of deafness.…”

Section: Discussionmentioning

confidence: 99%

Waardenburg syndrome

Konno¹,

Silm

2001

Acad Dermatol Venereol

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Waardenburg syndrome (WS) is caused by autosomal dominant mutations, and is characterized by pigmentary anomalies and various defects of neural crest derived tissues. We report a very interesting case of type 1 WS (WS 1) in an adult who presented all the symptoms characteristic of this syndrome. One particularly important clinical feature of WS is congenital hearing loss, which may severely handicap a child. A careful clinical description is useful to differentiate between various types of WS and other associated auditory-pigmentary syndromes. Type WS 1, characterized by dystopia canthorum, is caused by loss of function mutations in the PAX3 gene.

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“…Unfortunately, not every case expresses all clinical manifestations of complete WS and incomplete or “fruste forme” is commonly described. Type I WS is characterized by evidence of dystopia canthorum and the full symptomatology of the disease 13–15 , 20 , 23 , 29 , 30 (Fig. 1).…”

Section: Clinical Manifestationsmentioning

confidence: 99%

“…WS type I is characterized by evidence of dystopia canthorum and the full symptomatology of the disease 11 , 14 , 16 , 20 , 23 , 29 , 30 . The head circumference, clivus length, and facial depth are small in individuals affected with WSI 30 .…”

Section: Geneticsmentioning

confidence: 99%