We ascertained three consanguineous Pakistani families (PKDF291, PKDF335 and PKDF793) segregating nonsyndromic recessive hearing
loss. The hearing loss segregating in PKDF335 and PKDF793 is moderate to severe, whereas it is profound in PKDF291. The maximum
two-point LOD scores are 3.01 (D19S1034), 3.85 (D19S894) and 3.71 (D19S894) for PKDF291, PKDF335 and PKDF793, respectively.
Haplotype analyses of the three families define a 1.16 Mb region of overlap of the homozygous linkage intervals bounded by
markers D19S216 (20.01 cM) and D19S1034 (20.75 cM). These results define a novel locus,
DFNB72, on chromosome 19p13.3. There are at least 22 genes in the 1.16 Mb interval, including
PTPRS,
ZNRF4 and
CAPS. We identified no pathogenic variants in the exons and flanking intronic sequences of these three genes in affected members
of the DFNB72 families.
DFNB72 is telomeric to
DFNB68, the only other known deafness locus with statistically significant support for linkage to chromosome 19p.