Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F

K N Alagramam; H Yuan; M H Kuehn; C L Murcia; S Wayne; C R Srisailpathy; R B Lowry; R Knaus; L Van Laer; F P Bernier; S Schwartz; C Lee; C C Morton; R F Mullins; A Ramesh; G Van Camp; G S Hageman; R P Woychik; R J Smith; G S Hagemen

Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F

K N Alagramam, H Yuan, M H Kuehn, C L Murcia, S Wayne, C R Srisailpathy, R B Lowry, R Knaus, L Van Laer, F P Bernier, S Schwartz, C Lee, C C Morton, R F Mullins, A Ramesh, G Van Camp, G S Hageman, R P Woychik, R J Smith, G S Hagemen

Division of Evolution, Infection and Genomics

Case Western Reserve University

Research output: Contribution to journal › Article › peer-review

Abstract

We have determined the molecular basis for Usher syndrome type 1F (USH1F) in two families segregating for this type of syndromic deafness. By fluorescence in situ hybridization, we placed the human homolog of the mouse protocadherin Pcdh15 in the linkage interval defined by the USH1F locus. We determined the genomic structure of this novel protocadherin, and found a single-base deletion in exon 10 in one USH1F family and a nonsense mutation in exon 2 in the second. Consistent with the phenotypes observed in these families, we demonstrated expression of PCDH15 in the retina and cochlea by RT-PCR and immunohistochemistry. This report shows that protocadherins are essential for maintenance of normal retinal and cochlear function.

Original language	English
Pages (from-to)	1709-18
Number of pages	10
Journal	Human Molecular Genetics
Volume	10
Issue number	16
Publication status	Published - 1 Aug 2001

Keywords

Adult
Amino Acid Sequence
Animals
Blotting, Northern
Blotting, Western
Cadherins
Cochlea
DNA Mutational Analysis
Deafness
Female
Fetus
Gene Expression Profiling
Genetic Linkage
Humans
In Situ Hybridization, Fluorescence
Male
Mice
Molecular Sequence Data
Mutation
Pedigree
Polymorphism, Single-Stranded Conformational
Protein Precursors
Retina
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
Syndrome
Journal Article
Research Support, U.S. Gov't, P.H.S.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Alagramam, K. N., Yuan, H., Kuehn, M. H., Murcia, C. L., Wayne, S., Srisailpathy, C. R., Lowry, R. B., Knaus, R., Van Laer, L., Bernier, F. P., Schwartz, S., Lee, C., Morton, C. C., Mullins, R. F., Ramesh, A., Van Camp, G., Hageman, G. S., Woychik, R. P., Smith, R. J., & Hagemen, G. S. (2001). Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F. Human Molecular Genetics, 10(16), 1709-18.

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title = "Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F",

abstract = "We have determined the molecular basis for Usher syndrome type 1F (USH1F) in two families segregating for this type of syndromic deafness. By fluorescence in situ hybridization, we placed the human homolog of the mouse protocadherin Pcdh15 in the linkage interval defined by the USH1F locus. We determined the genomic structure of this novel protocadherin, and found a single-base deletion in exon 10 in one USH1F family and a nonsense mutation in exon 2 in the second. Consistent with the phenotypes observed in these families, we demonstrated expression of PCDH15 in the retina and cochlea by RT-PCR and immunohistochemistry. This report shows that protocadherins are essential for maintenance of normal retinal and cochlear function.",

keywords = "Adult, Amino Acid Sequence, Animals, Blotting, Northern, Blotting, Western, Cadherins, Cochlea, DNA Mutational Analysis, Deafness, Female, Fetus, Gene Expression Profiling, Genetic Linkage, Humans, In Situ Hybridization, Fluorescence, Male, Mice, Molecular Sequence Data, Mutation, Pedigree, Polymorphism, Single-Stranded Conformational, Protein Precursors, Retina, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Amino Acid, Syndrome, Journal Article, Research Support, U.S. Gov't, P.H.S.",

author = "Alagramam, \{K N\} and H Yuan and Kuehn, \{M H\} and Murcia, \{C L\} and S Wayne and Srisailpathy, \{C R\} and Lowry, \{R B\} and R Knaus and \{Van Laer\}, L and Bernier, \{F P\} and S Schwartz and C Lee and Morton, \{C C\} and Mullins, \{R F\} and A Ramesh and \{Van Camp\}, G and Hageman, \{G S\} and Woychik, \{R P\} and Smith, \{R J\} and Hagemen, \{G S\}",

year = "2001",

month = aug,

day = "1",

language = "English",

volume = "10",

pages = "1709--18",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "16",

}

Alagramam, KN, Yuan, H, Kuehn, MH, Murcia, CL, Wayne, S, Srisailpathy, CR, Lowry, RB, Knaus, R, Van Laer, L, Bernier, FP, Schwartz, S, Lee, C, Morton, CC, Mullins, RF, Ramesh, A, Van Camp, G, Hageman, GS, Woychik, RP, Smith, RJ & Hagemen, GS 2001, 'Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F', Human Molecular Genetics, vol. 10, no. 16, pp. 1709-18.

TY - JOUR

T1 - Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F

AU - Alagramam, K N

AU - Yuan, H

AU - Kuehn, M H

AU - Murcia, C L

AU - Wayne, S

AU - Srisailpathy, C R

AU - Lowry, R B

AU - Knaus, R

AU - Van Laer, L

AU - Bernier, F P

AU - Schwartz, S

AU - Lee, C

AU - Morton, C C

AU - Mullins, R F

AU - Ramesh, A

AU - Van Camp, G

AU - Hageman, G S

AU - Woychik, R P

AU - Smith, R J

AU - Hagemen, G S

PY - 2001/8/1

Y1 - 2001/8/1

N2 - We have determined the molecular basis for Usher syndrome type 1F (USH1F) in two families segregating for this type of syndromic deafness. By fluorescence in situ hybridization, we placed the human homolog of the mouse protocadherin Pcdh15 in the linkage interval defined by the USH1F locus. We determined the genomic structure of this novel protocadherin, and found a single-base deletion in exon 10 in one USH1F family and a nonsense mutation in exon 2 in the second. Consistent with the phenotypes observed in these families, we demonstrated expression of PCDH15 in the retina and cochlea by RT-PCR and immunohistochemistry. This report shows that protocadherins are essential for maintenance of normal retinal and cochlear function.

AB - We have determined the molecular basis for Usher syndrome type 1F (USH1F) in two families segregating for this type of syndromic deafness. By fluorescence in situ hybridization, we placed the human homolog of the mouse protocadherin Pcdh15 in the linkage interval defined by the USH1F locus. We determined the genomic structure of this novel protocadherin, and found a single-base deletion in exon 10 in one USH1F family and a nonsense mutation in exon 2 in the second. Consistent with the phenotypes observed in these families, we demonstrated expression of PCDH15 in the retina and cochlea by RT-PCR and immunohistochemistry. This report shows that protocadherins are essential for maintenance of normal retinal and cochlear function.

KW - Adult

KW - Amino Acid Sequence

KW - Animals

KW - Blotting, Northern

KW - Blotting, Western

KW - Cadherins

KW - Cochlea

KW - DNA Mutational Analysis

KW - Deafness

KW - Female

KW - Fetus

KW - Gene Expression Profiling

KW - Genetic Linkage

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - Male

KW - Mice

KW - Molecular Sequence Data

KW - Mutation

KW - Pedigree

KW - Polymorphism, Single-Stranded Conformational

KW - Protein Precursors

KW - Retina

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Sequence Homology, Amino Acid

KW - Syndrome

KW - Journal Article

KW - Research Support, U.S. Gov't, P.H.S.

M3 - Article

C2 - 11487575

SN - 0964-6906

VL - 10

SP - 1709

EP - 1718

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 16

ER -

Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F

Abstract

Keywords

UN SDGs

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