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Background: Congenital atrichia (CA) is a rare form of irreversible alopecia with an autosomal recessive mode of inheritance. This form of hair loss is mainly associated with mutations in the human hairless (HR) gene located at chromosome 8p21.3. An additional unique feature atrichia with papular lesions (APL) comprises keratin‐filled cysts known as papules. The present study aimed to uncover the underlying genetic causes of APL in two consanguineous Kashmiri families. Methods: In the present study, two consanguineous families of Kashmiri origin with APL displaying an autosomal recessive mode of inheritance were investigated. Whole exome and Sanger sequencing followed by bioinformatic studies, variant prioritization, Sanger validation and segregation analysis was performed to find the mutation. Results: A recurrent nonsense (NM_005144: c.2818C > T:p.Arg940*) mutation was detected in exon 13 of the human HR gene. Conclusions: Whole exome sequencing analysis has widely been used in the screening of single gene disorders mutations, both in research and diagnostic laboratories. Sanger sequencing alone for genes such as HR becomes expensive and time consuming. Instead, it is recommended that a patient is to screen by whole exome sequencing and then special attention first focuses on known genes of the APL phenotype. This is helpful for intime diagnosis, being more efficient and economic. The results obtained in the present study may contribute to prenatal diagnosis, carrier secreening and the genetic counseling of families with the APL phenotype in Kashmiri poplution. [ABSTRACT FROM AUTHOR]

Objectives The present study aimed to identify the genetic cause of non-syndromic primary failure of tooth eruption in a five-generation consanguineous Saudi family using whole-exome sequencing (WES) analysis. Design The family pedigree and phenotype were obtained from patient medical records. WES of all four affected family members was performed using the 51Mb SureSelect V4 library kit and then sequenced using the Illumina HiSeq2000 sequencing system. Sequence alignment, variant calling, and the annotation of single nucleotide polymorphisms and indels were performed using standard bioinformatics pipelines. The genotype of candidate variants was confirmed in all available family members by Sanger sequencing. Results Pedigree analysis suggested that the inheritance was autosomal recessive. WES of all affected individuals identified a novel homozygous variant in exon 8 of the parathyroid hormone 1 receptor gene ( PTH1R ) ( NM_000316 : c.611T>A: p.Val204Glu). Conclusion To the best of our knowledge, this is the first report of primary failure of eruption caused by a homozygous mutation in PTH1R . Our findings prove the application of WES as an efficient molecular diagnostics tool for this rare phenotype and further broaden the clinical spectrum of PTH1R pathogenicity. [ABSTRACT FROM AUTHOR]

A novel locus DFNB90 was mapped to 7p22.1-p15.3 by carrying out a genome scan in a multigenerational consanguineous family from Pakistan with autosomal recessive nonsyndromic hearing impairment (ARNSHI).DFNB90 is the eighth ARNSHI locus mapped to chromosome 7. A multipoint LOD score of 4.0 was obtained at a number of SNP marker loci spanning from rs1468996 (chromosome 7: 5.7 Mb) tors957960 (chromosome 7: 18.8 Mb). The 3-unit support interval and the region of homozygosity for DFNB90 spans from markers rs1553960 (chromosome 7: 4.9 Mb) to rs206198 (chromosome 7: 20.3 Mb). Candidate genes ACTB, BZW, OCM, MACC1, NXPH1, PRPS1L1, RAC1 and RPA3, which lie within the DFNB90 region, were sequenced and no potentially causal variants were identified. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]