#619810
Table of Contents
A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-84 (DFNA84) is caused by heterozygous mutation in the ATP11A gene (605868) on chromosome 13q34.
Autosomal dominant deafness-84 (DFNA84) is characterized by slowly progressive nonsyndromic sensorineural hearing loss. Onset is usually in the postlingual period, during the first or second decades, although both congenital and later onset has been reported. There is intrafamilial variation in disease severity, audiogram shape, and progression (summary by Pater et al., 2022).
Pater et al. (2022) reported a large 6-generation family from Newfoundland in which 16 individuals had progressive sensorineural hearing loss. The proband presented at age 13 years with progressive hearing loss and a sloping audiogram. His father presented with hearing loss in the first decade. Other affected family members had a variable age at onset: 2 failed newborn screening, whereas others reported hearing loss in the second or third decades. Subsequently, several individuals with postlingual-onset progressive hearing loss from 2 unrelated multigenerational Jewish Israeli families with origins in Uzbekistan (family A) and Afghanistan (family B) were identified. Most affected individuals had onset in the first decade, but later onset was also reported. Hearing loss began in high frequencies and progressed with age, with variable severity. The 46-year-old proband in family A showed severe sensorineural hearing loss and a sloping audiogram at age 39 years. The proband in family B was a 29-year-old woman with onset of hearing loss mainly affecting high frequencies at around age 17 years. Audiograms of affected individuals in all families were variably abnormal and showed hearing loss affecting all frequencies; the course of degeneration to severe or profound hearing loss was also variable, even within families.
The transmission pattern of DFNA84 in the families reported by Pater et al. (2022) was consistent with autosomal dominant inheritance.
By genomewide linkage analysis of a large family from Newfoundland with autosomal dominant deafness, Pater et al. (2022) found significant linkage to a 3.6-Mb region on chromosome 13q34 (LOD score of 4.77). This region overlaps that of DFNA33 (614211), suggesting that the 2 disorders may be caused by mutation in the same gene.
In affected members of 3 unrelated families with DFNA84, Pater et al. (2022) identified heterozygous mutations in the ATP11A gene (605868.0001 and 605868.0002). The mutations, which were found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in both families. Both mutations were complex genetic alterations causing abnormal splicing or resulting in a frameshift and premature termination. Both mutations affected the 3-prime UTR of several isoforms.
Pater, J. A., Penney, C., O'Rielly, D. D., Griffin, A., Kamal, L., Brownstein, Z., Vona, B., Vinkler, C., Shohat, M., Barel, O., French, C. R., Singh, S., and 16 others. Autosomal dominant non-syndromic hearing loss maps to DFNA33 (13q34) and co-segregates with splice and frameshift variants in ATP11A, a phospholipid flippase gene. Hum. Genet. 141: 431-444, 2022. [PubMed: 35278131, images, related citations] [Full Text]
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 13q34 | Deafness, autosomal dominant 84 | 619810 | Autosomal dominant | 3 | ATP11A | 605868 |
A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-84 (DFNA84) is caused by heterozygous mutation in the ATP11A gene (605868) on chromosome 13q34.
Autosomal dominant deafness-84 (DFNA84) is characterized by slowly progressive nonsyndromic sensorineural hearing loss. Onset is usually in the postlingual period, during the first or second decades, although both congenital and later onset has been reported. There is intrafamilial variation in disease severity, audiogram shape, and progression (summary by Pater et al., 2022).
Pater et al. (2022) reported a large 6-generation family from Newfoundland in which 16 individuals had progressive sensorineural hearing loss. The proband presented at age 13 years with progressive hearing loss and a sloping audiogram. His father presented with hearing loss in the first decade. Other affected family members had a variable age at onset: 2 failed newborn screening, whereas others reported hearing loss in the second or third decades. Subsequently, several individuals with postlingual-onset progressive hearing loss from 2 unrelated multigenerational Jewish Israeli families with origins in Uzbekistan (family A) and Afghanistan (family B) were identified. Most affected individuals had onset in the first decade, but later onset was also reported. Hearing loss began in high frequencies and progressed with age, with variable severity. The 46-year-old proband in family A showed severe sensorineural hearing loss and a sloping audiogram at age 39 years. The proband in family B was a 29-year-old woman with onset of hearing loss mainly affecting high frequencies at around age 17 years. Audiograms of affected individuals in all families were variably abnormal and showed hearing loss affecting all frequencies; the course of degeneration to severe or profound hearing loss was also variable, even within families.
The transmission pattern of DFNA84 in the families reported by Pater et al. (2022) was consistent with autosomal dominant inheritance.
By genomewide linkage analysis of a large family from Newfoundland with autosomal dominant deafness, Pater et al. (2022) found significant linkage to a 3.6-Mb region on chromosome 13q34 (LOD score of 4.77). This region overlaps that of DFNA33 (614211), suggesting that the 2 disorders may be caused by mutation in the same gene.
In affected members of 3 unrelated families with DFNA84, Pater et al. (2022) identified heterozygous mutations in the ATP11A gene (605868.0001 and 605868.0002). The mutations, which were found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in both families. Both mutations were complex genetic alterations causing abnormal splicing or resulting in a frameshift and premature termination. Both mutations affected the 3-prime UTR of several isoforms.
Pater, J. A., Penney, C., O'Rielly, D. D., Griffin, A., Kamal, L., Brownstein, Z., Vona, B., Vinkler, C., Shohat, M., Barel, O., French, C. R., Singh, S., and 16 others. Autosomal dominant non-syndromic hearing loss maps to DFNA33 (13q34) and co-segregates with splice and frameshift variants in ATP11A, a phospholipid flippase gene. Hum. Genet. 141: 431-444, 2022. [PubMed: 35278131] [Full Text: https://doi.org/10.1007/s00439-022-02444-x]
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