IntroductionMeier-Gorlin syndrome 7 (MGORS7) is a rare autosomal recessive disorder characterized by primordial dwarfism, craniosynostosis, and patellar aplasia, caused by pathogenic variants of CDC45. Here, we report a Chinese patient presenting with classic hallmarks of MGORS7 alongside atypical clinical features, including hearing and visual impairments.MethodsClinical and radiological data were collected. Whole-genome sequencing and Sanger sequencing were performed to identify and validate the causative variants. Their functional effects were investigated using an exon-trapping assay, and a literature review of previously reported MGORS7 cases was conducted.ResultsGenetic analysis identified two compound heterozygous CDC45 variants: c.1416C>T (p.H472=) and c.1559+2T>A, which are a recurrent variant in the East Asian population and a novel variant, respectively. Our exon-trapping assay indicated that c.1559+2T>A induced aberrant splicing, generating transcripts predicted to undergo nonsense-mediated mRNA decay. Additionally, growth hormone therapy was initiated in our patient, with a noted improvement in growth parameters in the initial assessment and without immediate complications. The literature review identified a total of 32 CDC45 variants in 29 patients with MGORS7, who showed high heterogeneity in clinical phenotypes.DiscussionOur study further expanded the mutational spectrum of CDC45 and provided a preliminary clinical observation suggesting that growth hormone therapy may be beneficial for growth retardation in patients with MGORS7.

BACKGROUND:Autosomal recessive spinocerebellar ataxia-13 is a rare multifactorial disorder characterized by physical disability, cerebellar ataxia, adaptive behavior, intellectual disability, response to sudden noise and light, sensation, skeletal, and oculomotor abnormalities. It affects both males and females equally. So far, only seven variants have been identified in the glutamate metabotropic receptor 1 ( GRM1 ) gene in 18 familial cases of Roma, Iranian, Pakistani, and Tunisian origins. METHODS:In the present study, we have investigated a large consanguineous family of Pakistani origin presenting severe phenotypes like intellectual disability, delayed developmental milestones, severe ataxia, and nonprogressive neuropathy. Whole exome sequencing was done, followed by Sanger sequencing. RESULTS:Sequence analysis revealed a novel homozygous deletion mutation (c.1715del) in the GRM1 gene (NM_001278064.2) that led to the substitution of Asn with Met at the 572 amino acid position, leading to frame shift and premature termination (p. Asn572MetfsTer4). CONCLUSION:This study raised the total number of GRM1 variants to eight and would be helpful in prenatal screening, genetic counseling, and carrier testing of other members in the Pakistani community.

BACKGROUND:Neurological disorders affect both the central and peripheral nervous systems, exhibiting broad genetic and clinical variability and posing a significant public health concern. These conditions range from common disorders, such as attention deficit disorder and epilepsy, to rare diseases like intellectual disability (ID) and white matter disorders. Exome sequencing (ES) has emerged as a powerful tool in diagnosing the genetic underpinnings of these disorders. ES demonstrated its feasibility as a cost-effective diagnostic pathway by identifying pertinent diagnostic outcomes in 29.4% of cases and being noticeably more cost-effective than conventional genetic diagnostic techniques. METHODOLOGY:This study investigated the genetic basis of three rare neurological disorders in three unrelated Pakistani families using ES. Each family presents with a distinct syndromic form of ID, associated with bilateral frontoparietal polymicrogyria (BFPP) (Family-1), Li-Ghorbani-Weisz-Hubshman syndrome (LIGOWS) (Family-2), or hypomyelination and congenital cataract (HCC) (Family-3). The functional consequences of the missense variants were investigated using bioinformatic prediction tools to confirm the pathogenicity. RESULTS:In Family-1 with BFPP, ES identified a novel homozygous missense variant ((NM_001145771.3): c.1579C > T; (NP_001139243.1): p.Pro527Ser) in ADGRG1, predicted to impact protein function. In Family-2 with LIGOWS, a novel homozygous missense variant ((NM_182958.4): c.649A > C; (NP_892003.2): p.Met217Leu) was found in KAT8. In Family-3 with HCC, a novel homozygous nonsense variant ((NM_032581.4): c.722T > G; (NP_115970.2): p.Leu241Ter) was identified in FAM126A, likely resulting in a truncated, nonfunctional protein. Families' structures and segregation analysis confirm disease condition segregating with autosomal recessive mode of inheritance. The functional consequences of the ADGRG1 and KAT8 missense variants were revealed as deleterious using bioinformatic prediction tools. CONCLUSIONS:We have identified novel pathogenic variants in ADGRG1, KAT8, and FAM126A in individuals with rare neurological disorders, thereby expanding the genetic and clinical spectrum of these conditions. This study reports, for the first time, an autosomal recessive inheritance pattern for a KAT8-related disorder, providing new insights into its genetic architecture.

Amelogenesis Imperfecta (AI) is a set of hereditary diseases affecting enamel development, leading to various types of enamel defects, potentially impacting oral health unassociated with other generalized defects. AI manifests in syndromic and non-syndromic forms and can be inherited through autosomal recessive, autosomal dominant, or X-linked inheritance patterns. Genetic studies have identified sequence variants in a number of genes (≥ 70) linked to both syndromic and non-syndromic AI, highlighting the genetic diversity underlying the condition. The current study involved clinical evaluation and exome sequencing, aimed at identifying the causative variants in four unrelated consanguineous Pakistani families presenting AI phenotypes. The exome sequencing results revealed a novel homozygous frameshift variant FAM20A : NM_017565.4, c.188dupA; p.(Asp63Glufs*17) in families A, B, and C while a nonsense homozygous variant WDR72 : NM_182758.4, c.2686C > T; p. (Arg896*) in family D. The segregation of both variants was confirmed by Sanger sequencing. Bioinformatics analysis predicted the pathogenicity of these genetic variants. These alterations suggest functional consequences, potentially impairing the FAM20A and WDR72 proteins and causing dental anomalies. This investigation significantly broadens our understanding of FAM20A and WDR72 ’s involvement in AI. Furthermore, this study highlights the genetic heterogeneity of AI (involving FAM20A and WDR72 in this study) within the Pakistani population.

Background: Postaxial polydactyly (PAP) is characterized by the development of extra digits at the fifth finger. It can occur as an isolated disease or a part of a syndrome. The genetic basis of nonsyndromic PAP has been linked to sequence variants in different genes. The aim of the present study was to identify the causative genetic variants in four Pakistani families demonstrating PAP. Methods: Causative genetic variants were identified using whole-exome sequencing and microsatellite mapping, followed by validation through Sanger sequencing. Further analysis was carried out through conservation, structural modeling, and 100-ns molecular dynamic simulations of GLI1. Results: Whole-exome and targeted sequencing in four families (A, B, C, and D) identified novel variants in the GLI1 (c.1013G>T; p.Cys338Phe), and GLI3 (c.2003C>T; p.Pro668Leu and c.4564delG; p.Ala1522ProfsTer2), and a recurrent variant in IQCE genes (c.895_904del; p.Val301SerfsTer8) linked to 7p22.3. All the variants were highly conserved across different species. Comparative analysis of the GLI1WT and GLI1Cys338Phe proteins revealed domain fluctuations leading to the loss of structurally and functionally important inter- and intramolecular interactions. The three-dimensional structural analysis of the GLI3 protein showed that the missense variant p. (Pro668Leu) disturbed the protein folding and intra-residue interaction, while the frameshift variant p. (Ala1522ProfsTer2) led to the loss of the C-terminus of the protein. Similarly, the IQCE structural analysis confirmed the loss of protein function due to frameshift and C-terminal deletion. Conclusion: This study has broadened the phenotypic and allelic spectrum of the genes associated with isolated PAP and strengthened the role of these genes in regulating limb development.

Dystrophic epidermolysis bullosa is a rare subtype of inherited epidermolysis bullosa, caused by variants in the collagen type VII alpha 1 chain (COL7A1) gene (MIM120120). Both autosomal dominant and recessive inheritance has been reported with variable phenotype. We investigated a Pakistani family with dystrophic epidermolysis bullosa via exome sequencing and identified a pathogenic nonsense variant in COL7A1 NM_000094 c.1573 C > T:p.(Arg525*). The inheritance pattern observed was consistent with a semi-dominant model, where heterozygous parents exhibited a mild phenotype, and homozygous children were more severely affected. For dystrophic epidermolysis bullosa, loss-of-function variants are typically associated with the autosomal recessive form, while missense variants are linked to the autosomal dominant form. A review of the literature suggests a semi-dominance pattern for some missense variants, particularly glycine substitutions, but this concept had not been formally recognized. This study highlights the importance of considering semi-dominant inheritance models for dystrophic epidermolysis bullosa and other Mendelian diseases with an autosomal recessive mode of inheritance, as it can significantly impact diagnosis and genetic counseling.

BACKGROUND:Acrocapitofemoral dysplasia (ACFD) is a rare autosomal recessive disorder, characterized by postnatal onset of disproportionate short stature with short limbs, brachydactyly, cone-shaped epiphysis, narrow thorax, and relatively large head. To date, only three homozygous missense mutations have been reported in the signaling amino terminal domain (201-308 amino acids) of the IHH gene in three ACFD families from Belgian, Dutch, and Turkish ethnicities. METHODS:In the present study, we have investigated two patients in a Pakistani family affected with ACFD. Whole exome sequencing (WES) followed by Sanger sequencing was carried out for mutational screening. The variant was further validated by in silico modeling and molecular dynamics simulation analysis. RESULTS:Data analysis revealed a novel homozygous missense variant [c.518C>A; p.(Ala173Asp)] in exon 2 of the IHH (NM_002181.4) gene. The variant segregated within the family and was not observed in unaffected ethnically matched controls. In silico modeling and dynamic simulation analysis revealed that the variant disturbed the core structure of the domain and destabilized the loop region and the region surrounding the variant. CONCLUSION:This study reports the first case of ACFD from Pakistan and identifies the fourth novel missense variant in the IHH gene that led to the broadening of the phenotypic and genotypic spectrum of ACFD.

Hereditary motor and sensory neuropathy (HMSN) refers to a group of inherited progressive peripheral neuropathies characterized by reduced nerve conduction velocity with chronic segmental demyelination and/or axonal degeneration. HMSN is highly clinically and genetically heterogeneous with multiple inheritance patterns and phenotypic overlap with other inherited neuropathies and neurodegenerative diseases. Due to this high complexity and genetic heterogeneity, this study aimed to elucidate the genetic causes of HMSN in Pakistani families using Whole Exome Sequencing (WES) for variant identification and Sanger sequencing for validation and segregation analysis, facilitating accurate clinical diagnosis. Families from Khyber Pakhtunkhwa with at least two members showing HMSN symptoms, who had not previously undergone genetic analysis, were included. Referrals for genetic investigations were based on clinical features suggestive of HMSN by local neurologists. WES was performed on affected individuals from each family, with Sanger sequencing used to validate and analyze the segregation of identified variants among family members. Clinical data including age of onset were assessed for variability among affected individuals, and the success rate of genetic diagnosis was compared with existing literature using proportional differences and Cohen’s h. WES identified homozygous pathogenic variants in GDAP1 (c.310 + 4 A > G, p.?), SETX (c.5948_5949del, p.(Asn1984Profs*30), IGHMBP2 (c.1591 C > A, p.(Pro531Thr) and NARS1 (c.1633 C > T, p.(Arg545Cys) as causative for HMSN in five out of nine families, consistent with an autosomal recessive inheritance pattern. Additionally, in families with HMSN, a SETX variant was found to cause cerebellar ataxia, while a NARS1 variant was linked to intellectual disability. Based on American College of Medical Genetics and Genomics criteria, the GDAP1 variant is classified as a variant of uncertain significance, while variants in SETX and IGHMBP2 are classified as pathogenic, and the NARS1 variant is classified as likely pathogenic. The age of onset ranged from 1 to 15 years (Mean = 5.13, SD = 3.61), and a genetic diagnosis was achieved in 55.56

Usher syndrome (USH) is a genetic disorder that is characterized by sensorineural hearing loss (HL) and visual abnormality, i.e., loss of night vision and side (peripheral) vision. Usher syndrome is categorized into four subtypes (USH1, USH2, USH3, USH4) on the basis of phenotypic spectrum. Profound hearing loss (HL), vestibular are flexia and language disturbance are typically associated with Usher type 1, while USH2 is linked with moderate to severe level of congenital HL. USH3 has late onset of deafness in life (referred to as "postlingual"), inconstant vestibular abnormality and onset of retinitis pigmentosa (RP) typically in 2nd decade of life. Patients with USH4 have no vestibular impairment and have late onset of retinitis pigmentosa (RP) and sensorineural hearing loss. Until now, 15 genetic loci have been reported to be linked with all types of USH. Among reported USH loci, nine are related to be involved in USH1, three in USH2, two in USH3 and one locus in USH4, respectively. Current review has described different types of Usher syndrome and their molecular genetics, and role of usher proteins in sensory organs. Moreover, we also suggested certain candidate genes for uncharacterized loci that may help the molecular geneticist to reach their target easily. Conclusion: The current catalogue of USH genetic data may assist in genetic counseling, genetic diagnosis, and genotype-phenotype correlation.

This study uses advanced computer vision (CV) and deep learning (DL) techniques to present a combined approach for extensive vehicle detection and number plate recognition. Improving the effectiveness and precision of traffic surveillance and administration systems is the main goal. The two primary parts of the suggested system are identification of number plates recognition and vehicle detection. The vehicle detection module uses rigid images or video streams to recognize along with monitor vehicles in real-time using innovative DL algorithms. Such limitations of system reliability are overcome through the application of CNN and object detection models in an integrated computer vision system that allows for reliable performance under a variety of environmental conditions including unfavorable lighting and weather situations. The goal of an identification plate recognition feature is to read and extract alphanumeric characters from license plates that have been detected. To precisely identify and interpret license plate data, this stage combines DL models with the use of optical character recognition (OCR) techniques. The system can adapt to different geographical locations by supporting changes in plate layouts, fonts, and positions. By combining these two modules, a complete intelligent transportation system solution is produced, offering useful information for applications such as congestion examination, safety, and assurance. Because of its modular architecture, the system is easily scalable and customizable, enabling it to be adjusted to various hardware configurations and surveillance scenarios. Using real-world scenarios and benchmark datasets, extensive experiments are conducted to assess the effectiveness of the proposed system. The outcomes show excellent efficiency and accuracy in tasks involving the detection of vehicles and number plate recognition. By promoting enhanced security, integrity, and general traffic management, the suggested integrated system advances innovative transportation methods.

Food dyes with a diverse set of colorants stimulate appetite and enhance aesthetic charm of food on table but at the same time these dyes contaminate the aquatic and biological ecosystems due to their cytotoxic and carcinogenic potentials. Herein, we report magnetite catalyzed removal of sunset yellow dye from water through catalytic degradation and ozonation. The magnetite catalyst revealed about 83% catalytic degradation and 92% catalytic ozonation performance toward sunset yellow dye at 100 and 25 min, respectively. Furthermore, the persulphate/magnetite/O-3 hybrid system revealed superior performance compared to the persulphate/magnetite under identical conditions. Kinetic studies revealed that the dye degradation data followed second-order kinetics, suggesting that the dye removal process is physicochemical in nature. This study further demonstrates that the persulfate/magnetite/O-3 hybrid system can efficiently decompose sunset yellow dye in aqueous solution compared to the Fenton's reagent and simple catalytic decomposition processes which is attributed to its unique structural features. [GRAPHICS] .

Glycosylphosphatidylinositols (GPIs) anchor over 150 proteins as GPI-anchored proteins (GPI-APs) with crucial roles in diverse biological processes. The highly conserved biosynthesis of GPI-APs involves precise steps with at least 21 genes, categorized as PIG and PGAP genes. Pathogenic variants in these genes are linked to human diseases, highlighting the importance of each biosynthesis step. PGAP2 stands out among these genes due to its association with an expanded clinical spectrum of neurodevelopmental disorder (NDD) phenotypes with biallelic pathogenic variants. We present four patients from two families, one consanguineous and the other nonconsanguineous, each displaying distinct clinical presentations, including intellectual disability, hyperphosphatasia, hearing impairment, and epilepsy, as well as craniofacial and digital anomalies. Genetic analyses revealed homozygous and novel compound heterozygous missense variants in PGAP2 in four affected individuals, confirming the molecular diagnosis of hyperphosphatasia with impaired intellectual development syndrome 3 (HPMRS3). Importantly, the three amino acids affected by missense variants exhibit complete conservation in 10 vertebrate species, illuminating their crucial role in the gene’s functionality. Protein modeling provided additional evidence for the pathogenicity of the three substitutions, demonstrating their detrimental impact on protein folding and putative protein-protein interactions, ultimately leading to impaired protein function. The four patients in our study displayed common phenotypic features, such as brachydactyly, camptodactyly, and syndactyly, which have not been previously documented in individuals with PGAP2 variants. Notably, the occurrence of macrocephaly in two affected brothers from a consanguineous Pakistani family represents a novel finding. These previously unreported digital anomalies, along with macrocephaly and the identification of novel compound heterozygous variants, contribute to the expansion of the phenotypic and genotypic spectrum of HPMRS3 associated with PGAP2 variants.

BackgroundPrelingual hearing impairment (HI) is genetically highly heterogenous. Early diagnosis and intervention are essential for psychosocial development. In this study we investigated a consanguineous family from Pakistan with autosomal recessive (AR) non-syndromic sensorineural HI (NSHI).MethodsA DNA sample from an HI member of a consanguineous Pakistani family segregating ARNSHL underwent exome sequencing. Using Sanger sequencing select variants were validated and tested for segregation using DNA samples from additional family members. We further investigated RNA expression data for the candidate gene in mouse and human inner ear and human inner ear organoids using data obtained from the gene Expression Analysis Resource.ResultsWe identified thrombospondin 1 (THBS1) as a new NSHI gene. A homozygous frameshift variant [c.1470del: p.(Ile491Serfs*45)] was observed in the three hearing-impaired and in the heterozygous state in three unaffected family members. Unlike for most ARNSHI, hearing-impaired individuals had audiograms with a sloping pattern, showing more pronounced HI in the mid and high frequencies (ranging from moderate to profound) compared to the low frequencies. RNA expression data indicates THBS1 is expressed during human inner ear development. Additionally, THBS1 is expressed in the cochlear epithelium and supporting cells of the mouse inner ear during embryonic and postnatal stages. Previously, THBS1 was demonstrated to affect hearing in knockout mice by influencing the formation and function of afferent synapses in the inner ear.ConclusionsOur findings highlight THBS1 as a potential novel candidate gene for human HI characterized by a sloping high-frequency audio profile. This discovery enhances our understanding of the genetic etiology of HI and will aid in advancing molecular diagnosis.

BackgroundIntellectual disability (ID) is a neurodevelopmental condition affecting around 2% of children and young adults worldwide, characterized by deficits in intellectual functioning and adaptive behavior. Genetic factors contribute to the development of ID phenotypes, including mutations and structural changes in chromosomes. Pathogenic variants in the HCFC1 gene cause X-linked mental retardation syndrome, also known as Siderius type X-linked mental retardation. The MN1 gene is necessary for palate development, and mutations in this gene result in a genetic condition called CEBALID syndrome. MethodsExome sequencing was used to identify the disease-causing variants in two affected families, A and B, from various regions of Pakistan. Affected individuals in these two families presented ID, developmental delay, and behavioral abnormalities. The validation and co-segregation analysis of the filtered variant was carried out using Sanger sequencing. ResultsIn an X-linked family A, a novel hemizygous missense variant (c.5705G > A; p.Ser1902Asn) in the HCFC1 gene (NM_005334.3) was identified, while in family B exome sequencing revealed a heterozygous nonsense variant (c.3680 G > A; p. Trp1227Ter) in exon-1 of the MN1 gene (NM_032581.4). Sanger sequencing confirmed the segregation of these variants with ID in each family. ConclusionsThe investigation of two Pakistani families revealed pathogenic genetic variants in the HCFC1 and MN1 genes, which cause ID and expand the mutational spectrum of these genes.

The current narrative review was planned to evaluate the quality of life of Pakistani cancer patients. Using relevant questionnaires and comparing global data over the last 2 decades, the review planned to explore artificial intelligence’s role in cancer care, and to develop strategies for better outcomes. The review yielded poor results and exposed huge and neglected gaps in the overall approach towards the management of cancer patients based on different tumour types and categories. A few experimental interventions demonstrated promising results and echoed the need for further clinical and non-clinical experimentation for negating poor quality of life outcomes. Unsurprisingly, not a single study in the literature analysed revealed a positive quality of life. A multi-pronged approach, therefore, must be brainstormed and safely implemented through experimentation of artificial intelligence and active coordination among healthcare bodies, finance/economic boards and welfare organisations that are active in countries like Pakistan to uplift the neglected quality of life domain among cancer patients, especially breast and oral cancers that have the highest incidences worldwide. Key Words: Quality of life, Neoplasms, Breast neoplasms, Mouth neoplasms.

Intellectual disability (ID) is a condition that varies widely in both its clinical presentation and its genetic underpinnings. It significantly impacts patients’ learning capacities and lowers their IQ below 70. The solute carrier (SLC) family is the most abundant class of transmembrane transporters and is responsible for the translocation of various substances across cell membranes, including nutrients, ions, metabolites, and medicines. The SLC13A3 gene encodes a plasma membrane-localized Na+/dicarboxylate cotransporter 3 (NaDC3) primarily expressed in the kidney, astrocytes, and the choroid plexus. In addition to three Na + ions, it brings four to six carbon dicarboxylates into the cytosol. Recently, it was discovered that patients with acute reversible leukoencephalopathy and a-ketoglutarate accumulation (ARLIAK) carry pathogenic mutations in the SLC13A3 gene, and the X-linked neurodevelopmental condition Christianson Syndrome is caused by mutations in the SLC9A6 gene, which encodes the recycling endosomal alkali cation/proton exchanger NHE6, also called sodium-hydrogen exchanger-6. As a result, there are severe impairments in the patient’s mental capacity, physical skills, and adaptive behavior. Two Pakistani families (A and B) with autosomal recessive and X-linked intellectual disorders were clinically evaluated, and two novel disease-causing variants in the SLC13A3 gene (NM 022829.5) and the SLC9A6 gene (NM 001042537.2) were identified using whole exome sequencing. Family-A segregated a novel homozygous missense variant (c.1478 C > T; p. Pro493Leu) in the exon-11 of the SLC13A3 gene. At the same time, family-B segregated a novel missense variant (c.1342G > A; p.Gly448Arg) in the exon-10 of the SLC9A6 gene. By integrating computational approaches, our findings provided insights into the molecular mechanisms underlying the development of ID in individuals with SLC13A3 and SLC9A6 mutations. We have utilized in-silico tools in the current study to examine the deleterious effects of the identified variants, which carry the potential to understand the genotype-phenotype relationships in neurodevelopmental disorders.

In this research, we propose an energy-management scheme for domestic users, which uses the load-shifting strategy of demand-side management (DSM). The research demonstrates that the energy sector’s circular debt problem from the viewpoint of a developing country can be solved by incorporating DSM. Circular debt is a chain reaction that arises when the balance between cost and energy supply collapses. Circular debt is an ongoing problem in Pakistan, where economic crises are continuously posing a threat to the energy sector. DSM is envisioned to address these concerns in a dynamic way thoroughly: introducing DSM can minimize circular debt, increase grid reliability, and smooth the supply–demand operation. Circular debt is directly linked with the subsidy offered by the government of Pakistan. As the cost of energy utilized by consumers increases, the subsidy also increases due to the direct link between the two entities. Therefore, the subsidy can be controlled by energy-consumption management with the adoption of DSM. This study addresses that by incorporating optimized cost solutions, circular debt can be regulated to improve the economy of the energy sector. A genetic algorithm is used as an optimization tool to manage demand and generate an optimal schedule under a dynamic electricity pricing signal. To support the utility, a solar system is used as a secondary energy source. Finally, the results show a curtailment in the payable costs at both the consumer and government ends, thus reducing the circular debt in the bigger picture. The reduction is 18% without and 41% with renewable energy support.

BACKGROUND:Congenital ichthyosis is a diverse group of keratinization disorders associated with generalized scaling of skin of varying severity. The non-syndromic forms of congenital ichthyosis are further grouped into common ichthyosis (ichthyosis vulgaris and X-linked ichthyosis), autosomal recessive congenital ichthyosis, and keratopathic ichthyosis.OBJECTIVE:To identify sequence variants involved in different forms of hereditary ichthyoses.METHODS:We studied eight families with different types of ichthyosis including four families with autosomal recessive congenital ichthyosis and four families with common ichthyosis. Whole exome sequencing and PCR based genotyping was carried out to find out the molecular basis of disease.RESULTS:In one family, a novel duplication sequence variant NM_002016.2:c.2767dupT; NP_002007.1:p.Ser923PhefsTer2 was identified in FLG gene; in four families a previously reported nonsense sequence variant NM_000359.3:c.232C>T; NP_002007.1:p.Arg78Ter was identified in TGM1 gene, while, in three families of X-linked recessive ichthyosis, the whole STS gene (NM_001320752.2; NP_001307681.2) regions were deleted.STUDY LIMITATION:Gene expression studies have not been performed that would have strengthened the findings of computational analysis.CONCLUSION:This study highlights the significance of the c.232C>T variant in the TGM1 gene as a possible founder mutation, complete STS gene deletion as reported previously in Pakistani population, while novel sequence variant in the FLG gene expands the spectrum of variations in this gene. These findings may be used for genetic counseling of the studied families.