Clinical And Genetic Analysis For Families With Non-syndromic Hereditary Hearing Loss Or Van Der Hoeve Syndrome

Deafness is a kind of ear disease which clinical feature is hearing loss or evendisappearance. General speaking, deafness is the structural or functional lesions ofauditory pathway to lead hearing loss. Deafness is a very common birth defects, also isthe most prevalent in sensorineural diseases. In average, there is1-3every1000newborns suffering from congenital deafness.27.8million people are hearing disabilityin the National Survey for disability in2006, and the number for newbornshas beenincreased by30thounsands per year.Most of the deafness is caused by both hereditary and environmental factors.Genetic deafness is divided into Syndromic hearing loss （SHL,30%） andNonsyndromic hearing loss （NSHL,70%）. SHL describes the deafness with theabnormalities of other organs and systems. However, NSHL presents the deafnesswithout the abnormalities of other organs and systems.In this study, we have successfully identified a novel hearing loss locus by usingmicrosatellite markers in a family with autosomal dominant non-syndromic deafness.We have also identified COL1A1gene mutation for a family with Van der HoeveSyndrome.PART1: Identification of gene underlying autosoma-dominant nonsyndromichearing loss in a Chinese familyWe have collected a family with autosomal dominant non-syndromic hereditaryhearing loss （DFNA） from Guangdong province. This family spanned three generationsand comprises18members. The affected members were showed prelingual, stable,bilateral moderate-severe neural hearing impairment involving all frequencies. Theoverall audiograms were flat. Prescreening of23DFNA loci with25known DFNAgenes by using microsatellite markers and linkage analysis and Gene sequence analysiswas performed. We mapped the locus to the region between D11S4089and D11S4157.By direct sequencing of the best candidate genes in mapping region, we identified anovel mutation c.5945C>A（p.A1982D）in TECTA gene.PART2: Mutation screening in one family with Van der Hoeve Syndrome Van der Hoeve Syndrome is a rare hereditary disease,which belongs toosteogenesis imperfect （OI）. There are three clinical features of Van der HoeveSyndrome: blue sclera, osteogenesis imperfect, conductive deafness. In this study, wehave collected a family with Van der Hoeve Syndrome, which showed bilateral bluesclera, repeated limb bone fracture and conduction deafness. Genomic DNA wasextracted from each individual and all exons of COL1A1gene were sequenced. Twopatients （the proband and his mother） in this family revealed a deletion of2bps in exon40（c.2910₂911delAG） of COL1A1gene, which created a premature stop codon at980amino acid. The mutation was not detected in the proband’s father. The mutation inCOL1A1gene is likely the causative defect in this family with Van der HoeveSyndrome. This mutation has not yet been reported in the COL1A1mutationdatabase．This result provides a solid basis for prenatal diagnosis in this family.