#618533
Table of Contents
A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-37 (DFNA37) is caused by heterozygous mutation in the COL11A1 gene (120280) on chromosome 1p21.
DFNA37 is an autosomal dominant form of early-onset postlingual progressive hearing impairment (Booth et al., 2019).
Booth et al. (2019) reported a large 4-generation family of European descent with postlingual, slowly progressive sensorineural hearing loss. Pure-tone audiometric evaluation showed mild to moderate hearing loss, although the finding of a significant threshold intercept at age 0 years at all frequencies except 8 kHz suggested the presence of a substantial congenital component (of 12 to 23 dB). The mean audiogram configuration developed from U-shaped to flat with advancing age up to about 40 years; at more advanced ages it remained flat or became very gently downsloping. Detailed analysis of the progression was expressed in dB per year, designated annual threshold deterioration (ATD).
Rad et al. (2021) studied 2 German families segregating autosomal dominant nonsyndromic prelingual sensorineural hearing loss. The proband in family 1 was a 37-year-old man who had stable downsloping moderate-to-severe high-frequency sensorineural hearing loss. His 7-year-old daughter failed newborn hearing screening but passed follow-up testing; at age 2 years she was diagnosed with severe hearing loss and was fitted with hearing aids. Serial audiometry showed stable, moderate-to-severe high-frequency sensorineural hearing loss. In family 2, the proband was a 31-year-old woman who had moderate sensorineural hearing loss in the middle and high frequencies since early childhood; she had worn hearing aids since age 27 years. Her son failed newborn hearing screening, with evoked-response audiometry showing mild hearing loss, whereas transient evoked otoacoustic emissions were bilaterally absent and distortion-product otoacoustic emissions were absent on the right and partially present on the left. At age 3.5 years, he had mild sensorineural hearing loss. None of the affected individuals had other symptoms.
Ciorba et al. (2021) reported a 6-year-old Italian boy who failed newborn hearing screening at birth and at 1 month. At age 10 months, audiologic examinations confirmed the presence of bilateral moderate-to-severe downsloping sensorineural hearing loss. His twin brother had the same audiologic findings, and both received bilateral hearing aids at age 16 months. Their older sister had postlingual bilateral moderate sensorineural hearing loss involving the middle to high frequencies. Family history revealed that moderate postlingual hearing loss was also present in their father and paternal grandmother; the paternal great-grandfather was also reported to have had hearing loss. Dysmorphology evaluation of the twins and their father was negative.
The transmission pattern of DFNA37 in the family reported by Booth et al. (2019) was consistent with autosomal dominant inheritance.
In affected members of a family with DFNA37, Booth et al. (2019) identified a heterozygous splice site mutation in the COL11A1 gene (120280.0013). The mutation, which was found by a combination of linkage analysis and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Using a minigene construct to express the mutation in cell lines, the authors showed that mutation resulted in the skipping of exon 5, causing an in-frame deletion and a peptide lacking residues 218 to 260 in the N-terminal propeptide. The mutation was predicted to affect all 5 transcripts of the gene, but possibly had a 'leaky' effect.
In affected individuals from 2 unrelated German families segregating autosomal dominant nonsyndromic prelingual sensorineural hearing loss, Rad et al. (2021) identified heterozygous splicing mutations in the COL11A1 gene (120280.0014 and 120280.0015, respectively).
In 5 affected members of a 4-generation Italian family with prelingual or postlingual sensorineural nonsyndromic hearing loss (NSHL) who were negative for mutations in the GJB2 (121011) and GJB6 (604418) genes as well as 96 other NSHL-associated genes, Ciorba et al. (2021) performed whole-exome sequencing and identified heterozygosity for a missense mutation in the COL11A1 gene (H165L; 120280.0016) that segregated fully with disease and was not found in public variant databases. The authors noted that the audiometric profiles of the affected family members were similar to those previously reported for individuals with COL11A1-associated hearing loss.
Booth, K. T., Askew, J. W., Talebizadeh, Z., Huygen, P. L. M., Eudy, J., Kenyon, J., Hoover, D., Hildebrand, M. S., Smith, K. R., Bahlo, M., kimberling, W. J., Smith, R. J. H., Azaiez, H., Smith, S. D. Splice-altering variant in COL11A1 as a cause of nonsyndromic hearing loss DFNA37. Genet. Med. 21: 948-954, 2019. [PubMed: 30245514, related citations] [Full Text]
Ciorba, A., Corazzi, V., Melegatti, M., Morgan, A., Pelliccione, G., Girotto, G., Bigoni, S. Non-syndromic sensorineural prelingual and postlingual hearing loss due to COL11A1 gene mutation. J. Int. Adv. Otol. 17: 81-83, 2021. [PubMed: 33605226, related citations] [Full Text]
Rad, A., Schade-Mann, T., Gamerdinger, P., Yanus, G. A., Schulte, B., Muller, M., Imyanitov, E. N., Biskup, S., Lowenheim, H., Tropitzsch, A., Vona, B. Aberrant COL11A1 splicing causes prelingual autosomal dominant nonsyndromic hearing loss in the DFNA37 locus. Hum. Mutat. 42: 25-30, 2021. [PubMed: 33169910, related citations] [Full Text]
ORPHA: 90635; DO: 0070601;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1p21.1 | Deafness, autosomal dominant 37 | 618533 | Autosomal dominant | 3 | COL11A1 | 120280 |
A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-37 (DFNA37) is caused by heterozygous mutation in the COL11A1 gene (120280) on chromosome 1p21.
DFNA37 is an autosomal dominant form of early-onset postlingual progressive hearing impairment (Booth et al., 2019).
Booth et al. (2019) reported a large 4-generation family of European descent with postlingual, slowly progressive sensorineural hearing loss. Pure-tone audiometric evaluation showed mild to moderate hearing loss, although the finding of a significant threshold intercept at age 0 years at all frequencies except 8 kHz suggested the presence of a substantial congenital component (of 12 to 23 dB). The mean audiogram configuration developed from U-shaped to flat with advancing age up to about 40 years; at more advanced ages it remained flat or became very gently downsloping. Detailed analysis of the progression was expressed in dB per year, designated annual threshold deterioration (ATD).
Rad et al. (2021) studied 2 German families segregating autosomal dominant nonsyndromic prelingual sensorineural hearing loss. The proband in family 1 was a 37-year-old man who had stable downsloping moderate-to-severe high-frequency sensorineural hearing loss. His 7-year-old daughter failed newborn hearing screening but passed follow-up testing; at age 2 years she was diagnosed with severe hearing loss and was fitted with hearing aids. Serial audiometry showed stable, moderate-to-severe high-frequency sensorineural hearing loss. In family 2, the proband was a 31-year-old woman who had moderate sensorineural hearing loss in the middle and high frequencies since early childhood; she had worn hearing aids since age 27 years. Her son failed newborn hearing screening, with evoked-response audiometry showing mild hearing loss, whereas transient evoked otoacoustic emissions were bilaterally absent and distortion-product otoacoustic emissions were absent on the right and partially present on the left. At age 3.5 years, he had mild sensorineural hearing loss. None of the affected individuals had other symptoms.
Ciorba et al. (2021) reported a 6-year-old Italian boy who failed newborn hearing screening at birth and at 1 month. At age 10 months, audiologic examinations confirmed the presence of bilateral moderate-to-severe downsloping sensorineural hearing loss. His twin brother had the same audiologic findings, and both received bilateral hearing aids at age 16 months. Their older sister had postlingual bilateral moderate sensorineural hearing loss involving the middle to high frequencies. Family history revealed that moderate postlingual hearing loss was also present in their father and paternal grandmother; the paternal great-grandfather was also reported to have had hearing loss. Dysmorphology evaluation of the twins and their father was negative.
The transmission pattern of DFNA37 in the family reported by Booth et al. (2019) was consistent with autosomal dominant inheritance.
In affected members of a family with DFNA37, Booth et al. (2019) identified a heterozygous splice site mutation in the COL11A1 gene (120280.0013). The mutation, which was found by a combination of linkage analysis and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Using a minigene construct to express the mutation in cell lines, the authors showed that mutation resulted in the skipping of exon 5, causing an in-frame deletion and a peptide lacking residues 218 to 260 in the N-terminal propeptide. The mutation was predicted to affect all 5 transcripts of the gene, but possibly had a 'leaky' effect.
In affected individuals from 2 unrelated German families segregating autosomal dominant nonsyndromic prelingual sensorineural hearing loss, Rad et al. (2021) identified heterozygous splicing mutations in the COL11A1 gene (120280.0014 and 120280.0015, respectively).
In 5 affected members of a 4-generation Italian family with prelingual or postlingual sensorineural nonsyndromic hearing loss (NSHL) who were negative for mutations in the GJB2 (121011) and GJB6 (604418) genes as well as 96 other NSHL-associated genes, Ciorba et al. (2021) performed whole-exome sequencing and identified heterozygosity for a missense mutation in the COL11A1 gene (H165L; 120280.0016) that segregated fully with disease and was not found in public variant databases. The authors noted that the audiometric profiles of the affected family members were similar to those previously reported for individuals with COL11A1-associated hearing loss.
Booth, K. T., Askew, J. W., Talebizadeh, Z., Huygen, P. L. M., Eudy, J., Kenyon, J., Hoover, D., Hildebrand, M. S., Smith, K. R., Bahlo, M., kimberling, W. J., Smith, R. J. H., Azaiez, H., Smith, S. D. Splice-altering variant in COL11A1 as a cause of nonsyndromic hearing loss DFNA37. Genet. Med. 21: 948-954, 2019. [PubMed: 30245514] [Full Text: https://doi.org/10.1038/s41436-018-0285-0]
Ciorba, A., Corazzi, V., Melegatti, M., Morgan, A., Pelliccione, G., Girotto, G., Bigoni, S. Non-syndromic sensorineural prelingual and postlingual hearing loss due to COL11A1 gene mutation. J. Int. Adv. Otol. 17: 81-83, 2021. [PubMed: 33605226] [Full Text: https://doi.org/10.5152/iao.2020.8179]
Rad, A., Schade-Mann, T., Gamerdinger, P., Yanus, G. A., Schulte, B., Muller, M., Imyanitov, E. N., Biskup, S., Lowenheim, H., Tropitzsch, A., Vona, B. Aberrant COL11A1 splicing causes prelingual autosomal dominant nonsyndromic hearing loss in the DFNA37 locus. Hum. Mutat. 42: 25-30, 2021. [PubMed: 33169910] [Full Text: https://doi.org/10.1002/humu.24136]
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