Association of serum protein electrophoresis with clinicopathological characteristics and its prognostic relevance in chronic lymphocytic leukaemia patients.

Objective: To assess the association of serum protein electrophoresis abnormalities with clinicopathological characteristics, and its impact on overall survival in chronic lymphocytic leukaemia patients. METHODS: The prospective study was conducted at Haematology and Immunology departments of the University of Health Sciences, Lahore, Pakistan, from 2019 to 2022, and comprised newly diagnosed chronic lymphocytic leukaemia patients. Lactate dehydrogenase and beta-2 microglobulin levels were measured by spectrophotometric principle, whereas serum protein electrophoresis was determined through commercially available capillary electrophoresis systems. Patients were followed up for 2 years post-diagnosis. Data was analysed using SPSS 21. RESULTS: Of the 50 patients, 40(80%) were males and 10(20%) were females. The overall mean age was 60±11 years. Serum protein electrophoresis was available for 40(80%) patients, and, among them, 12(30%) patients had abnormal levels, while 29(72.5%) required treatment. Overall response rate was 25(86.2%), and median two-year overall survival was 16.5 months (95% confidence interval: 10-20 months). Abnormal serum protein electrophoresis was significantly associated with Binet stage C, lower mean haemoglobin levels and higher median levels of lactate dehydrogenase and beta-2 microglobulin (p<0.05)). Regarding overall survival, the survival curves of chronic lymphocytic leukaemia patients with normal and abnormal serum protein electrophoresis status differed significantly (p=0.04). Conclusion: Abnormal serum protein electrophoresis could be considered a surrogate marker for advanced chronic lymphocytic leukaemia disease.

Detection of Partially Structural Collapse Using Long-Term Small Displacement Data from Satellite Images.

The development of satellite sensors and interferometry synthetic aperture radar (InSAR) technology has enabled the exploitation of their benefits for long-term structural health monitoring (SHM). However, some restrictions cause this process to provide a small number of images leading to the problem of small data for SAR-based SHM. Conversely, the major challenge of the long-term monitoring of civil structures pertains to variations in their inherent properties by environmental and/or operational variability. This article aims to propose new hybrid unsupervised learning methods for addressing these challenges. The methods in this work contain three main parts: (i) data augmentation by the Markov Chain Monte Carlo algorithm, (ii) feature normalization, and (iii) decision making via Mahalanobis-squared distance. The first method presented in this work develops an artificial neural network-based feature normalization by proposing an iterative hyperparameter selection of hidden neurons of the network. The second method is a novel unsupervised teacher-student learning by combining an undercomplete deep neural network and an overcomplete single-layer neural network. A small set of long-term displacement samples extracted from a few SAR images of TerraSAR-X is applied to validate the proposed methods. The results show that the methods can effectively deal with the major challenges in the SAR-based SHM applications.

Association of early donor chimerism status with survival outcomes in post allogeneic haematopoietic stem cell transplant patients of nonmalignant diseases.

OBJECTIVE: To highlight the association of early donor chimerism status at 2nd month with various survival outcomes. Method: The retrospective study was conducted at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, and comprised patient data from January 2011 to July 2016. Data related to participants who underwent human leukocyte antigen-matched transplants for bone marrow failure syndrome and beta thalassemia major. Short tandem repeat-based polymerase chain reaction was used to assess donor chimerism status. Overall survival, disease-free survival, relapse-free survival, and graft versus host disease-free survival rates were noted. Data was analysed using SPSS 23. RESULTS: Of the 106, 64(60.4%) had bone marrow failure syndrome and 42(39.6%) had beta thalassemia major. The overall median follow-up was 13.53 months (range: 1.81-62.73 months). Early donor chimerism status was associated with overall survival (p=0.02) and disease-free survival (p=0.01). Mixed donor chimerism was less hazardous in terms of overall survival (p=0.04) and disease-free survival (p=0.02). CONCLUSIONS: Early mixed donor chimerism contributed to optimal survival in nonmalignant disease.

Electrically controlled 1 × 2 tunable switch using a phase change material embedded silicon microring.

Phase change material Ge2Sb2Te5 (GST) has recently emerged as a highly promising candidate for photonic device applications owing to its high optical contrast, self-holding bi-stability, and fast material response. Here, we propose and analyze a 1×2 tunable switch using a GST embedded silicon microring resonator exploiting high optical contrast during GST phase change and a high thermo-optic coefficient of amorphous phase GST. Our device exhibits high extinction ratios of 25.57 dB and 18.75 dB at through and drop ports, respectively, with just a 1 µm long GST layer. The two states of the switch are realizable by electrically inducing phase change in GST. For post phase change from amorphous to crystalline and vice versa, the fall time down the 80% of phase transition temperature is ∼66ns and ∼45ns, respectively. The resonance wavelength shift per unit active length is 0.661 nm/µm, and the tuning efficiency is 1.16 nm/mW. The large wavelength tunability (4.63 nm) of the proposed switch makes it an attractive option for reconfigurable photonic integrated circuits.

Refining the role of phenology in regulating gross ecosystem productivity across European peatlands.

The role of plant phenology as a regulator for gross ecosystem productivity (GEP) in peatlands is empirically not well constrained. This is because proxies to track vegetation development with daily coverage at the ecosystem scale have only recently become available and the lack of such data has hampered the disentangling of biotic and abiotic effects. This study aimed at unraveling the mechanisms that regulate the seasonal variation in GEP across a network of eight European peatlands. Therefore, we described phenology with canopy greenness derived from digital repeat photography and disentangled the effects of radiation, temperature and phenology on GEP with commonality analysis and structural equation modeling. The resulting relational network could not only delineate direct effects but also accounted for possible effect combinations such as interdependencies (mediation) and interactions (moderation). We found that peatland GEP was controlled by the same mechanisms across all sites: phenology constituted a key predictor for the seasonal variation in GEP and further acted as a distinct mediator for temperature and radiation effects on GEP. In particular, the effect of air temperature on GEP was fully mediated through phenology, implying that direct temperature effects representing the thermoregulation of photosynthesis were negligible. The tight coupling between temperature, phenology and GEP applied especially to high latitude and high altitude peatlands and during phenological transition phases. Our study highlights the importance of phenological effects when evaluating the future response of peatland GEP to climate change. Climate change will affect peatland GEP especially through changing temperature patterns during plant phenologically sensitive phases in high latitude and high altitude regions.

Mid-infrared non-volatile silicon photonic switches using nanoscale Ge2Sb2Te5 embedded in silicon-on-insulator waveguides.

We propose and numerically analyze hybrid Si-Ge2Sb2Te5 strip waveguide switches for the mid-infrared wavelength of 2.1 µm. The switches investigated are of one input-one output (on-off) and one input-two outputs (directional coupler) types. The reversible transition between the switch states is achieved by inducing phase transition from crystalline to amorphous and vice-versa by application of voltage pulses. The approach of embedding the nanoscale active material Ge2Sb2Te5 within the Si waveguide is taken to enhance the interaction of light with the active region of the switches. The dimensions of the active regions of the switches are optimized to achieve low insertion loss, low switching energy and high extinction ratio. In the case of the on-off switch, an extinction ratio of 33.79 dB along with an extremely low insertion loss of 0.52 dB is achieved using an optimum Ge2Sb2Te5 length of only 0.92 µm. For the directional coupler switch, an extinction ratio of 10.33 dB and 5.23 dB is obtained in the cross and bar states respectively using an active length of 52 µm. These values of extinction ratio, which are otherwise 18.59 dB and 8.33 dB respectively, are due to the necessity of doping the Si beneath the Ge2Sb2Te5 to facilitate the electrical conduction needed for Joule heating. A suitable gap of 100 nm is maintained between the active and passive arm of the directional coupler switch. Electro-thermal co-simulations confirm that phase change occurs in the whole of the Ge2Sb2Te5 region in both types of switches.

European In-Situ Snow Measurements: Practices and Purposes.

In-situ snow measurements conducted by European institutions for operational, research, and energy business applications were surveyed in the framework of the European Cooperation in Science and Technology (COST) Action ES1404, called "A European network for a harmonised monitoring of snow for the benefit of climate change scenarios, hydrology, and numerical weather prediction". Here we present the results of this survey, which was answered by 125 participants from 99 operational and research institutions, belonging to 38 European countries. The typologies of environments where the snow measurements are performed range from mountain to low elevated plains, including forests, bogs, tundra, urban areas, glaciers, lake ice, and sea ice. Of the respondents, 93% measure snow macrophysical parameters, such as snow presence, snow depth (HS), snow water equivalent (SWE), and snow density. These describe the bulk characteristics of the whole snowpack or of a snow layer, and they are the primary snow properties that are needed for most operational applications (such as hydrological monitoring, avalanche forecast, and weather forecast). In most cases, these measurements are done with manual methods, although for snow presence, HS, and SWE, automatized methods are also applied by some respondents. Parameters characterizing precipitating and suspended snow (such as the height of new snow, precipitation intensity, flux of drifting/blowing snow, and particle size distribution), some of which are crucial for the operational services, are measured by 74% of the respondents. Parameters characterizing the snow microstructural properties (such as the snow grain size and shape, and specific surface area), the snow electromagnetic properties (such as albedo, brightness temperature, and backscatter), and the snow composition (such as impurities and isotopes) are measured by 41%, 26%, and 13% of the respondents, respectively, mostly for research applications. The results of this survey are discussed from the perspective of the need of enhancing the efficiency and coverage of the in-situ observational network applying automatic and cheap measurement methods. Moreover, recommendations for the enhancement and harmonization of the observational network and measurement practices are provided.

The effectiveness of script training to restore lost communication in a patient with Broca's aphasia.

Aphasia is considered as an acquired neurological disorder of communication, which is characterised by the symptoms on all levels of language dysfunction. The current study was planned to explore the outcomes of script training in a patient with Broca's aphasia through quantitative approach using a single-subject-multiple-baseline research design across behaviours. The probes were obtained during the baseline, treatment, maintenance and generalisation phases for tracking the spoken use of scripted content. All the probes were transcribed verbatim and no value of Cohen's Kappa Coefficient (K) was below 0.61, indicating robust inter-rater reliability. The subject learned all six scripts successively and over 80% of mastery level on all dependent variables was achieved. The largest effect size, above 10.1, was reported for the percent of intelligible scripted words (PISW). Script training was found to be an effective therapy for rejuvenating lost communication of patients with severe Broca's aphasia.

Recurrent Kimura Disease of the Inner Canthus With No Lymphadenopathy.

The Kimura disease is a benign rare inflammatory condition of the soft tissue, especially of the head and neck region presenting as painless nodule with or without lymphadenopathy. This condition with unknown etiology is seen mainly in Asian males, in their thirties. The authors' present a 39-year-old man with the Kimura disease in the inner canthus of his OS and no lymphadenopathy. The subcutaneous nodule was excised, and on histopathological study it was confirmed as the Kimura disease. He presented with a larger recurrence after 1 year. It was fixed to the underlying bone. Excision biopsy proved it to be the Kimura disease. To the authors' knowledge, this is the first report of the Kimura disease affecting ocular structures. The Kimura disease, although a rare condition, should be considered in the differential diagnosis of the primary and recurrent masses arising from the inner canthus of the eye.

Rare ß-Globin Gene Mutations in Pakistan.

The aim of this study was to analyze the rare ß-thalassemia (ß-thal) mutations in the Pakistani population. A total of 8716 unrelated Pakistani individuals having children with transfusion-dependent thalassemia were investigated by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) for the previously reported common and rare ß-thal mutations. Genomic sequencing of the ß-globin gene and its immediate 5' and 3' flanking regions was done where no known mutation was found. Out of the 8716 individuals studied, 88 (1.0%) were not characterized by ARMS-PCR. Genomic sequencing revealed that 67 (0.82%) individuals had 19 different ß-thal mutations including one novel mutation (HBB: c.136delT). The remaining 21 (0.26%) individuals did not show any mutation on the ß-globin gene and its immediate flanking regions. The characterized alleles included seven (0.09%) in the 5' untranslated region (5'UTR), 29 (0.35%) in the coding regions, and 31 (0.38%) in the splice junction regions. HBB: c.92+1G>A and HBB: c.113G>A were the most frequently seen rare mutations. The spectrum of ß-thal mutations in the Pakistani population is very diverse. In addition to the already reported mutations, another 19 different types of mutations were found. Interestingly, 21 individuals who had children with transfusion-dependent thalassemia and one known ß-thal mutation, did not show any mutation on the ß-globin gene. HBB: c.92+1G>A and HBB: c.113G>A are the most frequently seen rare mutations in Pakistan.

Novel VPS13B Mutations in Three Large Pakistani Cohen Syndrome Families Suggests a Baloch Variant with Autistic-Like Features.

BACKGROUND: Cohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits. METHODS: Clinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations. RESULTS: We identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population. CONCLUSION: We suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup.

DRY TAP: A DIAGNOSTIC ALERT FOR UNDERLYING BONE MARROW PATHOLOGY.

BACKGROUND: Dry tap is an annoying experience in bone marrow (BM) findings, especially in cases where the diagnosis may hinge on BM findings. This study was conducted to determine, on, the basis of bone marrow (BM) trephine biopsy, the frequency of various underlying conditions causing a dry tap, among different age groups. METHODS: It was a descriptive study carried out at PAF hospital Mianwali, Pakistan from 1" Jan 2009 to 31 Dec 2012. Record of all BM aspirations and trephine biopsies performed during 4 years was retrieved from hospital's laboratory. Total number of BM aspirations and trephines were counted and the subject's ages and genders recorded. Frequencies and percentages of patients with dry tap, in paediatric group (<15 years of age), young to middle-aged group (15-59 years) and the elderly (> or = 60 years) were calculated. Diagnoses of patients with dry tap made on BM biopsy were noted for each group and their frequencies calculated. RESULTS: Of 548 BM aspirations, dry tap was encountered in 52 (9.5%) cases. Acute lymphoblastic leukaemia (ALL) was the commonest cause of dry tap in paediatric age, seen in 6 (60%) of 10 children. In young to middle-aged group, non Hodgkin lymphoma (NHL) was the commonest cause, found in 6 (30%) of 20 cases. NHL and metastatic tumours, seen in 8 (36.4%) and 6 (27.3%) of 22 patients respectively, were the most frequent causes of dry tap in the elderly. CONCLUSION: Dry tap, in most of the cases, is like a diagnostic alert for the presence of an underlying BM pathology, nature of which depends upon age group.

Frequency of hereditary thrombophilia in women with recurrent pregnancy loss in Northern Pakistan.

AIM: Hereditary thrombophilia (HT) screening is performed as routine work-up of recurrent pregnancy loss (RPL) in Pakistan. In Northern Pakistan the prevalence of HT is not known. HT is not detected in the majority of RPL cases, especially in patients with ≤ 3 pregnancy losses (PL). The aim of this study was to determine the frequency of HT in women with RPL, and to find the prevalence of HT in patients with ≤ 3 PL and > 3 PL. MATERIAL AND METHODS: Lupus-anticoagulant-negative patients with unexplained RPL were screened for protein C, protein S, antithrombin, and factor V Leiden. RESULTS: A total of 315 patients with RPL were screened and 13 (4%) had evidence of HT. Protein C and protein S deficiency were detected in 6/140 (4.3%) women with > 3 PL and in 2/175 (1.1%) women with ≤ 3 PL. Antithrombin deficiency was detected in 2/140 (0.75%) women with > 3 PL and in no patients with ≤ 3 PL. Factor V Leiden was detected in 3/26 (12%) women with > 3 PL and in no patients with ≤ 3 PL. The prevalence of HT in patients with >3 PL was significantly higher than in patients with ≤ 3 PL (P = 0.002). We detected a strong association between HT and >3 PL (odds ratio 7.3; 95% confidence interval: 1.60-33.85) as compared to ≤ 3 PL. CONCLUSION: HT was detected in 4% of patients with RPL. The prevalence of HT in patients with > 3 PL is significantly higher than in patients with ≤ 3 PL.

High prevalence of protein C, protein S, antithrombin deficiency, and Factor V Leiden mutation as a cause of hereditary thrombophilia in patients of venous thromboembolism and cerebrovascular accident.

OBJECTIVES: To determine the frequency of Protein C, Protein S (PC & PS), antithrombin deficiency (AT III) and Factor V Leiden mutation (FVL) as a cause of thrombophilia in the patients with venous thromboembolism (VTE) and cerebrovascular accident (CVA). METHODS: It was an observational study conducted at Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan. All patients referred for thrombophilia screening from July 2009 to June 2012 were screened. Patients with evidence of VTE or CVA were screened for PC & PS, AT III deficiency, and FVL. RESULTS: Total 404 patients of age between 1-71 years mean 33 ± 14 with male to female ratio of 2.4:1 had evidence of thrombophilia. Two hundred eighteen (54%) patients presented with CVA, 116 (29%) with deep vein thrombosis (DVT), 42 (10.5%) with pulmonary embolism (PE), and 28 (7.5%) with portal or mesenteric vein thrombosis (PV). Protein C & S deficiency was detected in 35/404 (8.7%), ATIII in 9/404 (2%), and FVL in 25/173 patients (14.5%). The findings were suggestive of a significant association of FVL mutation for developing DVT (OR=11.0, 95% C I 4.6-26.3), CVA (OR=5.7, 95% C I 2.1-15.1), and PV (OR=5.4, 95% C I 1.3-21.9). PC & PS deficiency was a significant risk factor for developing PE (OR=3, 95% C I 0.8-11.4). CONCLUSION: FVL mutation and Protein C & S are the leading causes of thrombophilia with strong association of Factor V Leiden mutation as risk for developing DVT.

Spectrum of intra-ocular foreign bodies and the outcome of their management in Brunei Darussalam.

To review the etiologies, prognostic factors and treatment outcomes of intraocular foreign bodies (IOFBs) occurring in the population of Brunei Darussalam, and provide guidelines to prevent and manage such injuries. A retrospective review was performed for all cases of traumatic IOFBs managed in our centre during a 3-year period between May 2008 and April 2011. The mechanism of injury, management, complications and visual outcomes were analyzed. Majority of the patients were males (93 %) and the mean age was 36 years. The main causes of trauma were metal hammering and grass cutting (43 % each). Other causes include road traffic accidents and firecracker explosion (7 % each). The visual outcome was ≥6/18 in 50 % and 'No perception of light' in 29 %. Causes of poor visual outcome were retinal detachment with proliferative vitreoretinopathy (21 %), endophthalmitis (21 %) and globe maceration (7 %). Prognostic factors associated with significantly worse final visual outcome included posterior location of the IOFB (p = 0.05) and larger IOFB size (p < 0.001). The time from injury to surgery did not correlate with a worse visual prognosis. In Brunei Darussalam, the commonest causes of IOFBs are hammering metal and cutting grass using power tools. The visual outcome varies between 6/6 and NPL. Poor visual outcome is related to the severity of the initial ocular injury, posterior segment IOFB and endophthalmitis.

Prevalence of various mutations in beta thalassaemia and its association with haematological parameters.

OBJECTIVE: To determine the prevalence of various mutations in beta (beta) thalassaemia and its association with haematological parameters. METHODS: A descriptive cross sectional study was carried out in the Department of Haematology, Armed Forced Institute of Pathology (AFIP) from February 2009 to January 2010. A total of 515 carriers having beta thalassaemia mutations characterized by Multiplex amplification refractory mutation system (ARMS) were included in the study. Frequencies of different beta thalassaemia mutations were calculated. Mutations were analyzed for their haematological parameters which include total red blood cell count (TRBC), haemoglobin (Hb), mean cell volume (MCV), mean cell haemoglobin (MCH) and red cell distribution width (RDW). RESULTS: Frame shift (Fr) 8-9 was the most common mutation found in 183 (35.5%) of patients followed by intervening sequence 1-5 (IVSI-5) in 126 (24.5%) and Fr 41-42 in 76 (14.8%) while IVSII-1 was the least common mutation found in 1 patient. Fr 8-9 was also the commonest mutation in Punjabis and Pathans. Predominant mutation in other ethnic carriers was IVSI-5. Patients with Fr 8-9 mutation had the lowest mean MCV and MCH of 63.7fl and 19.1pg, of all the mutations. Patients with CAP+1 mutation had mean TRBC, Hb, MCV, MCH and RDW of 5.5 x 1012/L, 13.5g/dl, 78.0fl, 24.7pg and 41.9fl respectively. CONCLUSION: Fr 8-9 is the most common beta thalassaemia mutation with lowest red cell indices while CAP+1 mutation can present with normal red cell values therefore, a potential carrier should be screened for CAP+1 mutation by DNA analysis.

Guidelines on the laboratory diagnosis of congenital bleeding disorders in Pakistan.

Congenital bleeding disorders are found in all racial groups and are present worldwide. Among all of them haemophilia A, B and Von Willebrand's disease are the commonest and they are characterized by the low blood levels of factor VIII, IX and Von Willebrand's factor respectively. Severity of bleeding is proportional to the severity of factor deficiency. The diagnosis of bleeding disorders can be complex, and no single diagnostic tests are suitable for all patients. The guideline was developed after reviewing relevant publications, summarizing current understanding of bleeding disorders and classification, and present a consensus diagnostic recommendation based on analysis of the literature and expert opinion. They also suggest an approach for clinical and laboratory evaluation of individuals with bleeding symptoms, history of bleeding or conditions associated with increased bleeding risk. The document summarizes needs for improvement in laboratory testing and quality which is very much needed in Pakistan to make a correct diagnosis, train master trainers, identify complications of bleeding disorders in local population, increase awareness among masses, involve government in haemophilia care, education of patients and their families and health care community. It further enhances the need for research in bleeding disorders, including clinical research to obtain more objective information about bleeding symptoms, advancements in diagnostic and therapeutic tools.

Genetic Alterations, DNA Methylation, Alloantibodies and Phenotypic Heterogeneity in Type III von Willebrand Disease.

Type III von Willebrand disease is present in the Punjab province of Pakistan along with other inherited bleeding disorders like hemophilia. Cousin marriages are very common in Pakistan so genetic studies help to establish protocols for screening, especially at the antenatal level. Factors behind the phenotypic variation of the severity of bleeding in type III vWD are largely unknown. The study was conducted to determine Mutations/genetic alterations in type III von Willebrand disease and also to determine the association of different mutations, methylation status, ITGA2B/B3 mutations and alloimmunization with the severity of type III vWD. After informed consent and detailed history of the patients, routine tests and DNA extraction from blood, mutational analysis was performed by Next Generation Sequencing on Ion Torrent PGM. DNA methylation status was also checked with the help of PCR. In our cohort, 55 cases were detected with pathogenic mutations. A total of 27 different mutations were identified in 55 solved cases; 16 (59.2%) were novel. The mean bleeding score in truncating mutations and essential splice site mutations was relatively higher than weak and strong missense mutations. The mean bleeding score showed insignificant variation for different DNA methylation statuses of the VWF gene at the cg23551979 CpG site. Mutations in exons 7,10, 25, 28, 31, 43, and intron 41 splice site account for 75% of the mutations.

Novel mutations in the keratin-74 (KRT74) gene underlie autosomal dominant woolly hair/hypotrichosis in Pakistani families.

Autosomal dominant woolly hair (ADWH) is an inherited condition of tightly curled and twisted scalp hair. Recently, a mutation in human keratin-74 (KRT74) gene has been shown to cause this form of hereditary hair disorder. In the present study, we have described two families (A and B) having multiple individuals affected with autosomal dominant form of hair loss disorders. In family A, 10 individuals showed ADWH phenotype while in the family B, 14 individuals showed hypotrichosis of the scalp. Genotyping using polymorphic microsatellite markers showed linkage of both the families to type II keratin gene cluster on the chromosome 12q12-14.1. Mutation analysis of the KRT74 gene identified two novel mutations in the affected individuals of the families. The sequence analysis revealed a splice acceptor site mutation (c.IVS8-1G>A) in family A and a missense variant (c.1444G>A, p.Asp482Asn) in family B. Mutations identified in the present study extend the body of evidence implicating the KRT74 gene in the pathogenesis of autosomal dominant hair loss disorders.