Entry - #609439 - DEAFNESS, AUTOSOMAL RECESSIVE 48; DFNB48 - OMIM

 
ICD+
# 609439

DEAFNESS, AUTOSOMAL RECESSIVE 48; DFNB48


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number 		Inheritance Phenotype
mapping key 		Gene/Locus Gene/Locus
MIM number
15q25.1 Deafness, autosomal recessive 48 609439 AR 3 CIB2 605564
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
HEAD & NECK
Ears
- Hearing loss, congenital, profound (250-8,000 Hz)
MISCELLANEOUS
- Prelingual onset
- Hearing loss affects all frequencies
MOLECULAR BASIS
- Caused by mutation in the calcium- and integrin-binding protein 2 gene (CIB2, 605564.0001)
▲ Close
Deafness, autosomal recessive - PS220290 - 109 Entries
Location Phenotype Inheritance Phenotype
mapping key 		Phenotype
MIM number 		Gene/Locus Gene/Locus
MIM number
1p36.31-p36.13 Deafness, autosomal recessive 96 AR 2 614414 DFNB96 614414
1p36.31 Deafness, neurosensory, without vestibular involvement, autosomal dominant AR 3 609006 ESPN 606351
1p36.31 Deafness, autosomal recessive 36 AR 3 609006 ESPN 606351
1p34.3 Deafness, digenic, GJB2/GJB3 AR, DD 3 220290 GJB3 603324
1p31.3 ?Deafness, autosomal recessive 108 AR 3 617654 ROR1 602336
1p21.2 Deafness, autosomal recessive 32, with or without immotile sperm AR 3 608653 CDC14A 603504
1q23.2 Enlarged vestibular aqueduct, digenic AR 3 600791 KCNJ10 602208
1q43-q44 Deafness, autosomal recessive 45 AR 2 612433 DFNB45 612433
2p25.1-p24.3 Deafness, neurosensory, autosomal recessive 47 AR 2 609946 DFNB47 609946
2p23.3 Auditory neuropathy, autosomal recessive, 1 AR 3 601071 OTOF 603681
2p23.3 Deafness, autosomal recessive 9 AR 3 601071 OTOF 603681
2p16.1 Deafness, autosomal recessive 70, with or without adult-onset neurodegeneration AR 3 614934 PNPT1 610316
2p11.2 ?Deafness, autosomal recessive 88 AR 3 615429 ELMOD3 615427
2q23-q31 Deafness, autosomal recessive 27 AR 2 605818 DFNB27 605818
2q31.2 Deafness, autosomal recessive 59 AR 3 610220 PJVK 610219
3p25.3 {Deafness, autosomal recessive 12, modifier of} AR 3 601386 ATP2B2 108733
3p21.31 Deafness, autosomal recessive 6 AR 3 600971 TMIE 607237
3q13.33 Deafness, autosomal recessive 121 AR 3 620551 GPR156 610464
3q13.33 Deafness, autosomal recessive 42 AR 3 609646 ILDR1 609739
4p15.32 Deafness, autosomal recessive 117 AR 3 619174 CLRN2 618988
4p13 Deafness, autosomal recessive 25 AR 3 613285 GRXCR1 613283
4q12-q13.2 Deafness, autosomal recessive 55 AR 2 609952 DFNB55 609952
4q31.21 ?Deafness, autosomal recessive 26 AR 3 605428 GAB1 604439
5q13.2 Deafness, autosomal recessive 49 AR 3 610153 MARVELD2 610572
5q13.2 ?Deafness, autosomal recessive 112 AR 3 618257 BDP1 607012
5q21.1 Deafness, autosomal recessive 100 AR 3 618422 PPIP5K2 611648
5q23.3 Deafness, autosomal recessive 120 AR 3 620238 MINAR2 620215
5q32 ?Deafness, autosomal recessive 101 AR 3 615837 GRXCR2 615762
5q35.1 Enlarged vestibular aqueduct AR 3 600791 FOXI1 601093
6p25.2 ?Deafness, autosomal recessive 91 AR 3 613453 SERPINB6 173321
6p22.3 ?Deafness, autosomal recessive 66 AR 3 610212 DCDC2 605755
6p22.3 ?Deafness, autosomal recessive 104 AR 3 616515 RIPOR2 611410
6p21.32 Deafness, autosomal recessive 53 AR 3 609706 COL11A2 120290
6p21.31 Deafness, autosomal recessive 67 AR 3 610265 LHFPL5 609427
6p21.1 ?Deafness, autosomal recessive 103 AR 3 616042 CLIC5 607293
6q14.1 Deafness, autosomal recessive 37 AR 3 607821 MYO6 600970
6q26-q27 Deafness, autosomal recessive 38 AR 2 608219 DFNB38 608219
7p12.3 ?Deafness, autosomal recessive 44 AR 3 610154 ADCY1 103072
7q21.11 Deafness, autosomal recessive 39 AR 3 608265 HGF 142409
7q22.1 ?Deafness, autosomal recessive 61 AR 3 613865 SLC26A5 604943
7q22.3 Deafness, autosomal recessive 4, with enlarged vestibular aqueduct AR 3 600791 SLC26A4 605646
7q31 Deafness, autosomal recessive 14 AR 2 603678 DFNB14 603678
7q31 Deafness, autosomal recessive 17 AR 2 603010 DFNB17 603010
7q31.2 ?Deafness, autosomal recessive 97 AR 3 616705 MET 164860
7q34-q36 Deafness, autosomal recessive 13 AR 2 603098 DFNB13 603098
8p22-p21.3 Deafness, autosomal recessive 71 AR 2 612789 DFNB71 612789
8q22 Deafness, autosomal recessive 118, with cochlear aplasia AR 4 619553 DFNB118 619553
8q22.1 ?Deafness, autosomal recessive 109 AR 3 618013 ESRP1 612959
8q23.1-q23.2 Deafness, autosomal recessive 124 AR 3 620794 PKHD1L1 607843
9p23-p21.2 Deafness, autosomal recessive 83 AR 2 613685 DFNB83 613685
9q21.13 Deafness, autosomal recessive 7 AR 3 600974 TMC1 606706
9q32 Deafness, autosomal recessive 31 AR 3 607084 WHRN 607928
9q34.3 Deafness, autosomal recessive 79 AR 3 613307 TPRN 613354
10p12.1 Deafness, autosomal recessive 30 AR 3 607101 MYO3A 606808
10p11.23-q21.1 Deafness, autosomal recessive 33 AR 2 607239 DFNB33 607239
10q21.1 Deafness, autosomal recessive 23 AR 3 609533 PCDH15 605514
10q22.1 Deafness, autosomal recessive 12 AR 3 601386 CDH23 605516
10q24.31 Deafness, autosomal recessive 57 AR 3 618003 PDZD7 612971
11p15.5 Deafness autosomal recessive 106 AR 3 617637 EPS8L2 614988
11p15.1 Deafness, autosomal recessive 18A AR 3 602092 USH1C 605242
11p15.1 Deafness, autosomal recessive 18B AR 3 614945 OTOG 604487
11p14.3 ?Deafness, autosomal recessive 125 AR 3 620877 GAS2 602835
11p13-p12 Deafness, autosomal recessive 51 AR 2 609941 DFNB51 609941
11q13.2 Deafness, autosomal recessive 93 AR 3 614899 CABP2 607314
11q13.4 Deafness, autosomal recessive 63 AR 3 611451 LRTOMT 612414
11q13.5 Deafness, autosomal recessive 2 AR 3 600060 MYO7A 276903
11q14.1 ?Deafness, autosomal recessive 94 AR 3 618434 NARS2 612803
11q22.3 Deafness, autosomal recessive 24 AR 3 611022 RDX 179410
11q23.3 Deafness, autosomal recessive 111 AR 3 618145 MPZL2 604873
11q23.3 Deafness, autosomal recessive 21 AR 3 603629 TECTA 602574
11q25-qter Deafness, autosomal recessive 20 AR 2 604060 DFNB20 604060
12p13.2-p11.23 Deafness, autosomal recessive 62 AR 2 610143 DFNB62 610143
12p12.3 ?Deafness, autosomal recessive 102 AR 3 615974 EPS8 600206
12q14.3 Deafness, autosomal recessive 74 AR 3 613718 MSRB3 613719
12q21.31 Deafness, autosomal recessive 84B AR 3 614944 OTOGL 614925
12q21.31 Deafness, autosomal recessive 84A AR 3 613391 PTPRQ 603317
13q12.11 Deafness, autosomal recessive 1A AR, DD 3 220290 GJB2 121011
13q12.11 Deafness, digenic GJB2/GJB6 AR, DD 3 220290 GJB6 604418
13q12.11 Deafness, autosomal recessive 1B AR 3 612645 GJB6 604418
13q32.3 ?Deafness, autosomal recessive 122 AR 3 620714 TMTC4 618203
14q12 Deafness, autosomal recessive 5 AR 2 600792 DFNB5 600792
14q12 ?Deafness, autosomal recessive 110 AR 3 618094 COCH 603196
14q24.3 Deafness, autosomal recessive 35 AR 3 608565 ESRRB 602167
15q15.3 Deafness, autosomal recessive 16 AR 3 603720 STRC 606440
15q21.1 Deafness, autosomal recessive 119 AR 3 619615 AFG2B 619578
15q25.1 Deafness, autosomal recessive 48 AR 3 609439 CIB2 605564
16p13.3 Deafness, autosomal recessive 86 AR 3 614617 TBC1D24 613577
16p13.3 Deafness, autosomal recessive 116 AR 3 619093 CLDN9 615799
16p12.2 Deafness, autosomal recessive 22 AR 3 607039 OTOA 607038
16p11.2 ?Deafness, autosomal recessive 123 AR 3 620745 STX4 186591
16q23.1 Deafness, autosomal recessive 89 AR 3 613916 KARS1 601421
17p13.2 ?Deafness, autosomal recessive 115 AR 3 618457 SPNS2 612584
17p12-q11.2 Deafness, autosomal recessive 85 AR 2 613392 DFNB85 613392
17p11.2 Deafness, autosomal recessive 3 AR 3 600316 MYO15A 602666
17p11.2 Deafness, autosomal recessive 114 AR 3 618456 GRAP 604330
17q12 Deafness, autosomal recessive 99 AR 3 618481 TMEM132E 616178
17q25.1 Deafness, autosomal recessive 107 AR 3 617639 WBP2 606962
18p11.32-p11.31 Deafness, autosomal recessive 46 AR 2 609647 DFNB46 609647
18q21.1 Deafness, autosomal recessive 77 AR 3 613079 LOXHD1 613072
19p13.3 Deafness, autosomal recessive 15 AR 3 601869 GIPC3 608792
19p13.2 Deafness, autosomal recessive 68 AR 3 610419 S1PR2 605111
19q13.12 Deafness, autosomal recessive 76 AR 3 615540 SYNE4 615535
19q13.31-q13.32 Deafness, autosomal recessive 113 AR 3 618410 CEACAM16 614591
20q13.2-q13.3 Deafness, autosomal recessive 65 AR 2 610248 DFNB65 610248
21q22.13 Deafness, autosomal recessive 29 AR 3 614035 CLDN14 605608
21q22.3 Deafness, autosomal recessive 8/10 AR 3 601072 TMPRSS3 605511
21q22.3 ?Deafness, autosomal recessive 98 AR 3 614861 TSPEAR 612920
22q11.21-q12.1 Deafness, autosomal recessive 40 AR 2 608264 DFNB40 608264
22q13.1 Deafness, autosomal recessive 28 AR 3 609823 TRIOBP 609761
▲ Close

▼ TEXT

A number sign (#) is used with this entry because autosomal recessive deafness-48 (DFNB48) is caused by homozygous mutation in the CIB2 gene (605564) on chromosome 15q25.

▼ Description

DFNB48 is an autosomal recessive form of deafness. Affected individuals have prelingual onset of severe to profound sensorineural hearing loss affecting all frequencies (summary by Riazuddin et al., 2012).


▼ Mapping

By linkage analysis in 5 large consanguineous Pakistani families with nonsyndromic deafness segregating as an autosomal recessive trait, Ahmad et al. (2005) mapped the phenotype locus to chromosome 15q23-q25.1. Analysis in 1 of the families demonstrated linkage of the deafness locus, designated DFNB48, to D15S1005 (lod score of 8.6 at theta = 0), and a critical linkage interval of approximately 7 cM was defined between D15S216 and D15S1041. Affected individuals had bilateral profound congenital hearing loss.

Ahmed et al. (2009) sequenced the TLE3 gene within the DFNB48 locus but did not identify any pathogenic alleles.


▼ Molecular Genetics

In affected members of 54 Pakistani families with autosomal recessive deafness-48, Riazuddin et al. (2012) identified a homozygous mutation in the CIB2 gene (F91S; 605564.0001). Haplotype analysis indicated a founder effect. Two additional homozygous CIB2 mutations were found in other families with DFNB48 (C99W, 605564.0002 and I123T, 605564.0003). Transfection of the F91S and C99W mutations in COS-7 cells decreased or abolished the ability of CIB2 to decrease ATP-induced calcium release from the cell compared to wildtype, whereas transfection of the I123T mutation increased the ability of CIB2 to decrease calcium release compared to wildtype. These findings suggested that the mutations had an effect on CIB2 calcium-binding or buffering activity, and indicated that loss of this gene results in defects in calcium regulation.


▼ Population Genetics

Riazuddin et al. (2012) estimated that CIB2 mutations may account for up to 7.25% of Pakistani families with autosomal recessive deafness.


▼ REFERENCES

  1. Ahmad, J., Khan, S. N., Khan, S. Y., Ramzan, K., Riazuddin, S., Ahmed, Z. M., Wilcox, E. R., Friedman, T. B., Riazuddin, S. DFNB48, a new nonsyndromic recessive deafness locus, maps to chromosome 15q23-q25.1. Hum. Genet. 116: 407-412, 2005. [PubMed: 15711797, related citations] [Full Text]

  2. Ahmed, Z. M., Riazuddin, S., Khan, S. N., Friedman, P. L., Riazuddin, S., Friedman, T. B. USH1H, a novel locus for type I Usher syndrome, maps to chromosome 15q22-23. Clin. Genet. 75: 86-91, 2009. [PubMed: 18505454, images, related citations] [Full Text]

  3. Riazuddin, S., Belyantseva, I. A., Giese, A. P. J., Lee, K., Indzhykulian, A. A., Nandamuri, S. P., Yousaf, R., Sinha, G. P., Lee, S., Terrell, D., Hegde, R. S., Ali, R. A., and 19 others. Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. Nature Genet. 44: 1265-1271, 2012. [PubMed: 23023331, images, related citations] [Full Text]


Contributors:
Cassandra L. Kniffin - updated : 10/15/2012
Cassandra L. Kniffin - updated : 2/25/2009
Creation Date:
Marla J. F. O'Neill : 6/24/2005
Edit History:
carol : 06/21/2016
terry : 11/6/2012
carol : 10/15/2012
ckniffin : 10/15/2012
wwang : 2/25/2009
carol : 6/24/2005

# 609439

DEAFNESS, AUTOSOMAL RECESSIVE 48; DFNB48


ORPHA: 90636;   DO: 0110505;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number 		Inheritance Phenotype
mapping key 		Gene/Locus Gene/Locus
MIM number
15q25.1 Deafness, autosomal recessive 48 609439 Autosomal recessive 3 CIB2 605564

TEXT

A number sign (#) is used with this entry because autosomal recessive deafness-48 (DFNB48) is caused by homozygous mutation in the CIB2 gene (605564) on chromosome 15q25.

Description

DFNB48 is an autosomal recessive form of deafness. Affected individuals have prelingual onset of severe to profound sensorineural hearing loss affecting all frequencies (summary by Riazuddin et al., 2012).


Mapping

By linkage analysis in 5 large consanguineous Pakistani families with nonsyndromic deafness segregating as an autosomal recessive trait, Ahmad et al. (2005) mapped the phenotype locus to chromosome 15q23-q25.1. Analysis in 1 of the families demonstrated linkage of the deafness locus, designated DFNB48, to D15S1005 (lod score of 8.6 at theta = 0), and a critical linkage interval of approximately 7 cM was defined between D15S216 and D15S1041. Affected individuals had bilateral profound congenital hearing loss.

Ahmed et al. (2009) sequenced the TLE3 gene within the DFNB48 locus but did not identify any pathogenic alleles.


Molecular Genetics

In affected members of 54 Pakistani families with autosomal recessive deafness-48, Riazuddin et al. (2012) identified a homozygous mutation in the CIB2 gene (F91S; 605564.0001). Haplotype analysis indicated a founder effect. Two additional homozygous CIB2 mutations were found in other families with DFNB48 (C99W, 605564.0002 and I123T, 605564.0003). Transfection of the F91S and C99W mutations in COS-7 cells decreased or abolished the ability of CIB2 to decrease ATP-induced calcium release from the cell compared to wildtype, whereas transfection of the I123T mutation increased the ability of CIB2 to decrease calcium release compared to wildtype. These findings suggested that the mutations had an effect on CIB2 calcium-binding or buffering activity, and indicated that loss of this gene results in defects in calcium regulation.


Population Genetics

Riazuddin et al. (2012) estimated that CIB2 mutations may account for up to 7.25% of Pakistani families with autosomal recessive deafness.


REFERENCES

  1. Ahmad, J., Khan, S. N., Khan, S. Y., Ramzan, K., Riazuddin, S., Ahmed, Z. M., Wilcox, E. R., Friedman, T. B., Riazuddin, S. DFNB48, a new nonsyndromic recessive deafness locus, maps to chromosome 15q23-q25.1. Hum. Genet. 116: 407-412, 2005. [PubMed: 15711797] [Full Text: https://doi.org/10.1007/s00439-004-1247-y]

  2. Ahmed, Z. M., Riazuddin, S., Khan, S. N., Friedman, P. L., Riazuddin, S., Friedman, T. B. USH1H, a novel locus for type I Usher syndrome, maps to chromosome 15q22-23. Clin. Genet. 75: 86-91, 2009. [PubMed: 18505454] [Full Text: https://doi.org/10.1111/j.1399-0004.2008.01038.x]

  3. Riazuddin, S., Belyantseva, I. A., Giese, A. P. J., Lee, K., Indzhykulian, A. A., Nandamuri, S. P., Yousaf, R., Sinha, G. P., Lee, S., Terrell, D., Hegde, R. S., Ali, R. A., and 19 others. Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. Nature Genet. 44: 1265-1271, 2012. [PubMed: 23023331] [Full Text: https://doi.org/10.1038/ng.2426]


Contributors:
Cassandra L. Kniffin - updated : 10/15/2012
Cassandra L. Kniffin - updated : 2/25/2009

Creation Date:
Marla J. F. O'Neill : 6/24/2005

Edit History:
carol : 06/21/2016
terry : 11/6/2012
carol : 10/15/2012
ckniffin : 10/15/2012
wwang : 2/25/2009
carol : 6/24/2005



NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2025 Johns Hopkins University.

NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2025 Johns Hopkins University.
Printed: March 15, 2025