Mapping of a new autosomal recessive nonsyndromic hearing loss locus (DFNB32) to chromosome 1p13.3-22.1.
Approximately 80% of the hereditary hearing loss is nonsyndromic. Isolated deafness is the most genetically heterogeneous trait. We have ascertained 10 individuals from a large consanguineous Tunisian family with congenital profound autosomal recessive deafness. All affected individuals are otherwise healthy. Genotype analysis excluded linkage to known recessive deafness loci in this family. Following a genome wide screening, a linkage was detected only with locus D1S206 on chromosome 1, thereby defining a novel deafness locus, DFNB32. In order to confirm linkage and for fine mapping the genetic interval, 12 individuals belonging to this family were added and 19 microsatellite markers were tested. A maximum two-point lodscore of 4.96 was obtained at a new polymorphic marker D1S21401. Haplotype analysis defined a 16 Mb critical region between D1S2868 and afmb014zb9. The interval of DFNB32 locus overlap with DFNA37 locus and the Marshall and Stickler syndromes locus. The entire coding region of COL11A1, responsible of the later syndromes, was screened and no mutation was observed. Towards the identification of the DFNB32 gene, a search on the Human Cochlear cDNA Library and EST Database was done. The genes corresponding to the ESTs found in the DFNB32 interval are being screened for deafness-causing mutations.
Masmoudi
Saber
S
Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine Sfax, Tunisie.
Tlili
Abdelaziz
A
Majava
Marja
M
Ghorbel
Abdel Monem
AM
Chardenoux
Sébastien
S
Lemainque
Arnaud
A
Zina
Zeineb Ben
ZB
Moala
Jihene
J
Männikkö
Minna
M
Weil
Dominique
D
Lathrop
Mark
M
Ala-Kokko
Leena
L
Drira
Mohamed
M
Petit
Christine
C
Ayadi
Hammadi
H
D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D020224:Expressed Sequence Tags; D005260:Female; D005808:Genes, Recessive; D005819:Genetic Markers; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree
D005819:Genetic Markers