Ain Quratul, Nazli Sabiha, Riazuddin Saima, Jaleel Ateeq-ul, Riazuddin S Amer, Zafar Ahmad U, Khan Shaheen N, Husnain Tayyab, Griffith Andrew J, Ahmed Zubair M, Friedman Thomas B, Riazuddin Sheikh
National Centre of Excellence in Molecular Biology, University of the Punjab, 87-West Canal Bank Road, Thokar Niaz Baig, Lahore, 53700, Pakistan.
Hum Genet. 2007 Dec;122(5):445-50. doi: 10.1007/s00439-007-0418-z. Epub 2007 Aug 10.
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.
我们确定了三个患非综合征性隐性听力损失的巴基斯坦近亲家庭(PKDF291、PKDF335和PKDF793)。PKDF335和PKDF793中分离出的听力损失为中度至重度,而PKDF291中的听力损失为极重度。PKDF291、PKDF335和PKDF793的最大两点连锁对数分别为3.01(D19S1034)、3.85(D19S894)和3.71(D19S894)。对这三个家庭的单倍型分析确定了一个1.16 Mb的重叠区域,该区域为以标记D19S216(20.01 cM)和D19S1034(20.75 cM)为界的纯合连锁区间。这些结果在19号染色体p13.3上定义了一个新的位点DFNB72。在这个1.16 Mb的区间内至少有22个基因,包括PTPRS、ZNRF4和CAPS。我们在DFNB72家庭的患病成员中未发现这三个基因的外显子和侧翼内含子序列中的致病变异。DFNB72位于DFNB68的端粒位置,DFNB68是另一个已知的耳聋位点,有统计学显著支持与19号染色体p区连锁。