PMID- 27440999
OWN - NLM
STAT- MEDLINE
DCOM- 20180115
LR  - 20220318
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 22
DP  - 2016
TI  - Genetic analysis of Tunisian families with Usher syndrome type 1: toward 
      improving early molecular diagnosis.
PG  - 827-35
AB  - PURPOSE: Usher syndrome accounts for about 50% of all hereditary deaf-blindness 
      cases. The most severe form of this syndrome, Usher syndrome type I (USH1), is 
      characterized by profound congenital sensorineural deafness, vestibular 
      dysfunction, and retinitis pigmentosa. Six USH1 genes have been identified, 
      MYO7A, CDH23, PCDH15, USH1C, SANS, and CIB2, encoding myosin VIIA, cadherin-23, 
      protocadherin-15, harmonin, scaffold protein containing ankyrin repeats and a 
      sterile alpha motif (SAM) domain, and calcium- and integrin-binding member 2, 
      respectively. METHODS: In the present study, we recruited four Tunisian families 
      with a diagnosis of USH1, together with healthy unrelated controls. Affected 
      members underwent detailed audiologic and ocular examinations. We used the North 
      African Deafness (NADf) chip to search for known North African mutations 
      associated with USH. Then, we selected microsatellite markers covering USH1 known 
      loci to genotype the DNA samples. Finally, we performed DNA sequencing of three 
      known USH1 genes: MYO7A, PCDH15, and USH1C. RESULTS: Four biallelic mutations, 
      all single base changes, were found in the MYO7A, USH1C, and PCDH15 genes. These 
      mutations consist of a previously reported splicing defect c.470+1G>A in MYO7A, 
      three novel variants, including two nonsense (p.Arg3X and p.Arg134X) in USH1C and 
      PCDH15, respectively, and one frameshift (p.Lys615Asnfs*6) in MYO7A. CONCLUSIONS: 
      We found a remarkable genetic heterogeneity in the studied families with USH1 
      with a variety of mutations, among which three were novel. These novel mutations 
      will be included in the NADf mutation screening chip that will allow a higher 
      diagnosis efficiency of this extremely genetically heterogeneous disease. 
      Ultimately, efficient molecular diagnosis of USH in a patient's early childhood 
      is of utmost importance, allowing better educational and therapeutic management.
FAU - Ben-Rebeh, Imen
AU  - Ben-Rebeh I
AD  - Laboratoire de Procedes de criblage moleculaire et cellulaire, Centre de 
      Biotechnologie de Sfax, Universite de Sfax, Tunisie.
FAU - Grati, Mhamed
AU  - Grati M
AD  - Unite de Genetique et Physiologie de l'Audition, INSERM UMRS 1120, Institut 
      Pasteur, Paris, France.
FAU - Bonnet, Crystel
AU  - Bonnet C
AD  - INSERM UMRS 1120, Institut de la Vision, Paris, France.
FAU - Bouassida, Walid
AU  - Bouassida W
AD  - Service d'Ophtalmologie, C.H.U. H. Bourguiba de Sfax, Tunisie.
FAU - Hadjamor, Imen
AU  - Hadjamor I
AD  - Laboratoire de Procedes de criblage moleculaire et cellulaire, Centre de 
      Biotechnologie de Sfax, Universite de Sfax, Tunisie.
FAU - Ayadi, Hammadi
AU  - Ayadi H
AD  - Laboratoire de Procedes de criblage moleculaire et cellulaire, Centre de 
      Biotechnologie de Sfax, Universite de Sfax, Tunisie.
FAU - Ghorbel, Abdelmonem
AU  - Ghorbel A
AD  - Service d'O.R.L., C.H.U.H. Bourguiba de Sfax, Tunisie.
FAU - Petit, Christine
AU  - Petit C
AD  - Unite de Genetique et Physiologie de l'Audition, INSERM UMRS 1120, Institut 
      Pasteur, Paris, France; INSERM UMRS 1120, Institut de la Vision, Paris, France; 
      College de France, Paris, France.
FAU - Masmoudi, Saber
AU  - Masmoudi S
AD  - Laboratoire de Procedes de criblage moleculaire et cellulaire, Centre de 
      Biotechnologie de Sfax, Universite de Sfax, Tunisie.
LA  - eng
PT  - Journal Article
DEP - 20160719
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (CDHR15, human)
RN  - 0 (Cadherin Related Proteins)
RN  - 0 (Cadherins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Codon, Nonsense)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (MYO7A protein, human)
RN  - 0 (Myosin VIIa)
RN  - 0 (USH1C protein, human)
RN  - EC 3.6.4.1 (Myosins)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*genetics
MH  - Adolescent
MH  - Adult
MH  - Cadherin Related Proteins
MH  - Cadherins/*genetics
MH  - Cell Cycle Proteins
MH  - *Codon, Nonsense
MH  - Consanguinity
MH  - Cytoskeletal Proteins
MH  - DNA Mutational Analysis
MH  - Electroretinography
MH  - Female
MH  - *Frameshift Mutation
MH  - Genetic Testing
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Diagnostic Techniques
MH  - Myosin VIIa
MH  - Myosins/*genetics
MH  - Pedigree
MH  - Sequence Analysis, DNA
MH  - Tunisia
MH  - Usher Syndromes/*diagnosis/*genetics
MH  - Young Adult
PMC - PMC4950652
EDAT- 2016/07/22 06:00
MHDA- 2018/01/16 06:00
PMCR- 2016/01/01
CRDT- 2016/07/22 06:00
PHST- 2015/12/30 00:00 [received]
PHST- 2016/07/16 00:00 [accepted]
PHST- 2016/07/22 06:00 [entrez]
PHST- 2016/07/22 06:00 [pubmed]
PHST- 2018/01/16 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 68 [pii]
PST - epublish
SO  - Mol Vis. 2016 Jul 19;22:827-35. eCollection 2016.