ORPHA: 231169;
Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
---|---|---|---|---|---|---|
1p36.31 | ?Usher syndrome, type 1M | 618632 | Autosomal recessive | 3 | ESPN | 606351 |
A number sign (#) is used with this entry because of evidence that Usher syndrome type 1M (USH1M) is caused by homozygous mutation in the ESPN gene (606351) on chromosome 1p36. One such family has been reported.
Usher syndrome type 1M (USH1M) is characterized by prelingual sensorineural hearing loss, vestibular dysfunction, and retinitis pigmentosa (Ahmed et al., 2018).
For a general phenotypic description and discussion of genetic heterogeneity of Usher syndrome, see USH1 (276900).
Ahmed et al. (2018) studied a large, multiply consanguineous Pakistani family (PKDF1051) in which 22 individuals over 2 generations had bilateral profound prelingual sensorineural hearing loss, vestibular dysfunction, and progressive impairment of vision. Onset of independent ambulation was delayed to 2.5 years of age or older, and tandem gain and Romberg testing confirmed vestibular dysfunction. In addition, all affected individuals reported night vision problems, and funduscopy in the 5 clinically evaluated family members revealed an irregular retinal contour, temporal lipofuscin flecks, and disc pallor with normal retinal vessels. Electroretinography (ERG) showed diminished scotopic rod and scotopic combined responses, with relative preservation of photopic responses, consistent with early signs of retinitis pigmentosa. Noting that a 42-year-old affected individual did not show bone spicules or attenuated blood vessels on funduscopy, and had largely intact cone function on ERG, the authors considered the phenotype in this family to represent an atypical form of USH1.
In a large Pakistani family (PKDF1051) with hearing loss, vestibular dysfunction, and retinitis pigmentosa, negative for linkage to known USH loci, Ahmed et al. (2018) performed a genomewide screen and found suggestive linkage to markers on chromosome 1p36.32-p36.22. Haplotype analysis using STR markers revealed a 9.83-cM interval of homozygosity delimited by markers D1S2660 and D1S450. A maximum 2-point lod score of 3.79 (theta = 0) was obtained for the marker D1S214. The locus was designated 'USH1M.'
The transmission pattern of Usher syndrome type 1M in the family reported by Ahmed et al. (2018) was consistent with autosomal recessive inheritance.
In a large, multiply consanguineous Pakistani family with hearing loss, vestibular dysfunction, and retinitis pigmentosa mapping to chromosome 1p36 at a critical interval overlapping the locus for autosomal recessive nonsyndromic hearing loss (DFNB36; 609006) caused by mutation in the ESPN gene, Ahmed et al. (2018) screened ESPN and identified homozygosity for an in-frame 18-bp deletion (606351.0008). The mutation segregated with disease in the family and was not found in 224 ethnically matched chromosomes from the ExAC database or in the NHLBI-ESP database.
Ahmed, Z. M., Jaworek, T., Sarangdhar, G. N., Zheng, L., Gul, K., Khan, S. N., Friedman, T. B., Sisk, R. A., Bartles, J. R., Riazuddin, S., Riazuddin, S. Inframe deletion of human ESPN is associated with deafness, vestibulopathy and vision impairment. J. Med. Genet. 55: 479-488, 2018. [PubMed: 29572253] [Full Text: https://doi.org/10.1136/jmedgenet-2017-105221]