Missense Mutations in the CTSC Gene in Saudi Families Segregating Papillon-Lefèvre Syndrome

No abstract available.

Whole genome sequencing instead of whole exome sequencing is required to identify the genetic causes of polycystic ovary syndrome in Pakistani families

Background and Objective: Polycystic Ovary Syndrome [PCOS] is the major cause of infertility in females. PCOS is a complex and multifactorial disease, genetic and environmental factors being important predisposing factors. Diagnosis of PCOS is difficult due to the complexity of this disease; hence, better diagnostic tests are required to improve its management. Aim of the study was to elucidate the genetic causes of PCOS in three Pakistani families

Methods: Three Pakistani families segregating PCOS in an apparently autosomal recessive mode were recruited. Whole genome Single Nucleotide Polymorphism [SNP] genotyping and Whole Exome Sequencing [WES] were carried out to identify the candidate genes

Results: SNP genotypes data analyses identified multiple regions of homozygosity on different chromosomes. WES was performed in affected members of the family. Screening for pathogenic mutations in homozygous regions failed to detect any mutation/variant of interest

Conclusion: PCOS is multifactorial and complex disease so variants in the coding as well as in non-coding regions may be the genetic causes of the disease. To elucidate the genetic cause[s] of the PCOS, Whole Genome Sequencing [WGS] is recommended to cover both coding and non?coding regions of the genome

Intragenic deletion mutation in the gene desmoglein 4 underlies autosomal recessive hypotrichosis in six consanguineous families

Objectives: Localized autosomal recessive hypotrichosis is a non-syndromic human hair loss disorder, affecting scalp, eyebrows and eyelashes, and other parts of the body. Six consanguineous families with this form of hair loss disorder were investigated at both the clinical and molecular levels

Methods: Linkage in six families with twenty-one affected members was tested by genotyping microsatellite markers linked to autosomal recessive hypotrichosis loci including localized autosomal recessive hypotrichosis [LAH] 1, 2 and 3. Sequence analysis of the entire coding and splice sites of the gene DSG4 was performed to search for the disease-causing mutation

Results: Genotyping established linkage in families to the DSG4 gene at LAH1 locus on chromosome 18q21.1. Sequence analysis detected an intragenic deletion mutation [Ex5_8 del] in affected members of all six families

Conclusion: Identification of recurrent mutation in six additional Pakistani families strengthens the body of evidence that this is an ancestral mutation that is widespread among different Pakistani ethnic groups

Recurrent mutation in CDMP1 in a family with Grebe chondrodysplasia: broadening the phenotypic manifestation of syndrome in Pakistani population

Grebe syndrome [OMIM-200700] is a very rare type of acromesomelic dysplasia with autosomal recessive inheritance. We studied a Pakistani family with two affected individuals having typical features of Grebe chondrodysplasia. Patients were observed with short and deformed limbs having a proximo-distal gradient of severity. Hind-limbs were more severely affected than fore-limbs. Digits on autopods were very short and nonfunctional. Index subject also had nearsightedness. However, symptoms in the craniofacial and axial skeleton were minimal. Genetic analysis revealed four base pair insertion mutation [c.1114insGAGT] in gene coding cartilage-derived morphogenetic protein-1 [CDMP1]. This mutation was predicted to cause premature stop codon. The clinical presentation in this study broadens the range of phenotypes associated with CDMP1 mutation in Pakistani population