Novel mutations of MYO7A and USH1G in Israeli Arab families with Usher syndrome type 1.
OBJECTIVE
This study investigated the genetic basis for Usher syndrome type 1 (USH1) in four consanguineous Israeli Arab families.


METHODS
Haplotype analysis for all known USH1 loci was performed in each family. In families for which haplotype analysis was inconclusive, we performed genome-wide homozygosity mapping using a single nucleotide polymorphism (SNP) array. For mutation analysis, specific primers were used to PCR amplify the coding exons of the MYO7A, USH1C, and USH1G genes including intron-exon boundaries. Mutation screening was performed with direct sequencing.


RESULTS
A combination of haplotype analysis and genome-wide homozygosity mapping indicated linkage to the USH1B locus in two families, USH1C in one family and USH1G in another family. Sequence analysis of the relevant genes (MYO7A, USH1C, and USH1G) led to the identification of pathogenic mutations in all families. Two of the identified mutations are novel (c.1135-1147dup in MYO7A and c.206-207insC in USH1G).


CONCLUSIONS
USH1 is a genetically heterogenous condition. Of the five USH1 genes identified to date, USH1C and USH1G are the rarest contributors to USH1 etiology worldwide. It is therefore interesting that two of the four Israeli Arab families reported here have mutations in these two genes. This finding further demonstrates the unique genetic structure of the Israeli population in general, and the Israeli Arab population in particular, which due to high rates of consanguinity segregates many rare autosomal recessive genetic conditions.
The Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel.
Leah
L
Rizel
Christine
C
Safieh
Stavit A
SA
Shalev
Eedy
E
Mezer
Haneen
H
Jabaly-Habib
Ziva
Z
Ben-Neriah
Elena
E
Chervinsky
Daniel
D
Briscoe
Tamar
T
Ben-Yosef
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000483:Alleles; D018912:Arabs; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D003241:Consanguinity; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007438:Introns; D007557:Israel; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D052245:Usher Syndromes / Q000208:ethnology / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D009419:Nerve Tissue Proteins; C118970:USH1C protein, human; C477452:USH1G protein, human; D009218:Myosins