In a survey of mental retardation in an inbred Amish community, Eldridge et al. (1968) observed 4 of 7 sibs in a family (2 males, 2 females) who also had deafness and myopia. The extent of intellectual impairment ... In a survey of mental retardation in an inbred Amish community, Eldridge et al. (1968) observed 4 of 7 sibs in a family (2 males, 2 females) who also had deafness and myopia. The extent of intellectual impairment was difficult to evaluate. Sensory deprivation might have been a main factor. Ohlsson (1963) described deafness and severe myopia in 3 boys in a sibship of 7. One was stated to be of somewhat low intelligence. All 3 plus 3 other sibs and the mother had albuminuria or hematuria. Ohlsson (1963) concluded that the family did not have Alport syndrome (104200). Tekin et al. (2013) studied 2 families with deafness and high myopia. One was a consanguineous Old Order Amish family in which 3 sibs had congenital high myopia, with refraction error ranging from -7.25 to -10.25 diopters corrected by glasses, and prelingual-onset moderate to severe bilateral sensorineural hearing loss necessitating hearing aids. Their parents had low myopia with onset in their youth, and normal hearing. The second family was a consanguineous Turkish family in which 4 sibs had high myopia, with refraction error ranging from -6.0 to -11.0 diopters, and prelingual-onset moderate to profound sensorineural hearing loss. Their parents and 2 unaffected sibs did not have hearing loss; the father and 2 unaffected sibs had mild adult-onset myopia of less than -2 diopters. Affected individuals in both families did not exhibit delays in gross motor development, and none had balance problems, vertigo, dizziness, or spontaneous or positional nystagmus. CT scan of the temporal bone was normal in 1 affected individual from each family. Clinical examination confirmed the absence of additional findings, with normal facial appearance and normal neurologic, connective tissue, and ocular manifestations. None of the affected individuals had retinitis pigmentosa.
In a consanguineous Old Order Amish family with deafness and myopia mapping to chromosome 13q31, Tekin et al. (2013) analyzed candidate genes as well as microRNAs and other potentially functional molecules within the disease interval, and identified a ... In a consanguineous Old Order Amish family with deafness and myopia mapping to chromosome 13q31, Tekin et al. (2013) analyzed candidate genes as well as microRNAs and other potentially functional molecules within the disease interval, and identified a nonsense mutation in the SLITRK6 gene (Q414X; 609681.0001) that segregated with disease in the family. The mutation was not found in the dbSNP135 or 1000 Genomes Project database or in 450 controls of European ancestry; only a single heterozygous carrier was detected in 80 Amish controls. In parallel, whole-exome sequencing was performed in 2 affected individuals from a consanguineous Turkish family with deafness and myopia, which revealed homozygosity for a different nonsense mutation in SLITRK6 (S297X; 609681.0002) that cosegregated with disease in the family and was not found in 330 Turkish controls. Analysis of the SLITRK6 gene in 177 multiplex families with nonsyndromic autosomal recessive deafness, in some of which myopia was also present, identified a Greek family with 2 affected brothers who were homozygous for a third nonsense mutation (R181X; 609681.0003); the parents were heterozygous for the mutation, which was not found in 300 Greek controls. Screening for the R181X and S297X mutations in 370 probands from the United States with nonsyndromic sensorineural hearing loss identified no sequence variants.