Intellectual disability (ID) is a highly heterogeneous genetic condition with more than a thousand genes described so far. By exome sequencing of two consanguineous families presenting hallmark features of ID, we identified two homozygous variants in two genes previously associated with autosomal recessive ID: NDST1 (c.1966G>A; p.Asp656Asn) and METTL23 (c.310T>C; p.Phe104Leu). The segregation of the variants was validated by Sanger sequencing in all family members. In silico homology modeling of wild-type and mutated proteins revealed substantial changes in the secondary structure of both proteins, indicating a possible effect on function. The identification and validation of new pathogenic NDST1 and METTL23 variants in two cases of autosomal recessive ID further highlight the importance of these genes in proper brain function and development.

Distal arthrogryposis (DA) is a heterogeneous sub-group of arthrogryposis multiplex congenita (AMC), mostly characterized by having congenital contractures affecting hands, wrists, feet, and ankles. Distal arthrogryposis is mostly autosomal dominantly inherited, while only one sub-type DA type 5D is inherited in an autosomal recessive manner. Clinically, DA5D is described having knee extension contractures, micrognathia, distal joint contractures, clubfoot, ptosis, contractures (shoulders, elbows, and wrists), and scoliosis. Using whole exome sequencing (WES) followed by Sanger sequencing, we report on a first familial case of DA5D from Pakistani population having a novel biallelic missense mutation (c.158C>A, p.Pro53Leu) in the ECEL1 gene. Our result support that homozygous mutations in ECEL1 causes DA5D and expands the clinical and allelic spectrum of ECEL1 related contracture syndromes.

The term autosomal recessive congenital ichthyosis (ARCI) is the subgroup of ichthyosis, which describes a highly heterogeneous group of genetic disorders of the skin characterized by cornification and defective keratinocytes differentiation associated with mutations in at least 14 genes including PNPLA1. To study the molecular basis of the Pakistani kindreds (A and B) affected by ARCI, whole-exome sequencing (WES) in the DNA samples of affected members was performed followed by Sanger sequencing of the candidate gene to hunt down the disease-causing sequence variant/s. WES data analysis led to the identification of a novel nonsense sequence variant (c.892C>T; p.Arg298*, family A) and a recurrent missense variant (c.102C>A; p.Asp34Glu, family B) in PNPLA1 mapped to the ARCI locus in chromosome 6p21.31. Validation and cosegregation analysis of the variants in the remaining family members of the respective families were confirmed by Sanger sequencing. The current investigation expands the spectrum of PNPLA1 mutations and helps establish the proper clinico-genetic diagnosis and correct genotype-phenotype correlation.

Background: Polydactyly is a prevalent digit abnormality characterized by having extra digits/toes. Mutations in eleven known genes have been associated to cause nonsyndromic polydactyly: GLI3, GLI1, ZRS regulating LMBR1, IQCE, ZNF141, PITX1, MIPOL1, FAM92A, STKLD1, KIAA0825, and DACH1.Method: A single affected family member (IV-4) was subjected to whole-exome sequencing (WES) to identify the causal gene. Bi-directional Sanger sequencing was performed to segregate the identified variant within the family. In silico analysis was performed to investigate the effect of the variant on DNA binding properties.Results: whole-exome sequencing identified a bi-allelic missense variant (c.1010C > T; p. Ser337Leu) in exon nine of GLI1 gene located on chromosome 12q13.3. With the use of Sanger sequencing, the identified variant segregated perfectly with the disease phenotype. Furthermore, in silico analysis of this DNA binding protein revealed that the variant weakened the DNA binding interaction, resulting in indecorous GLI1 function.Conclusion: Herein, we report a novel variant in GLI1 gene, causing autosomal recessive post-axial polydactyly type A (PAPA) type 8. This confirms the critical role of GLI1 in digit development and might help in genotype–phenotype correlation in the future.

Objectives: Microorganisms produce optically single bioactive natural products; the process is cheap as compared to chemical synthesis and environmentally friendly. Geodin 1 was isolated from the soft coral-derived fungus Aspergillus sp. It has a broad range of biological activities such as antiviral, antimicrobial, glucose stimulator for rat adipocytes, enhancement of fibrinolytic and cytotoxic activities, and is a subunit of the first nonpeptide and inhibitory active galanin receptor. In this work, we studied the effects of sodium chloride (NaCl) salt concentration on the production of geodin 1 and improved its yield to a multi-gram quantity through media optimization from a marine-derived fungus Aspergillus sp. Methods: The fungal strain was cultivated at various concentrations of NaCl salt in rice medium and extracted after different intervals of time. Results: The yield of geodin 1 was 137.2 mg/L at optimal conditions. The optimal conditions for the high yield of geodin 1 were found as rice medium with 2.0% NaCl salt and 3 weeks incubation at room temperature. Conclusions: The concentration of NaCl salt greatly affects the yield of geodin and hence its biosynthetic pathway.