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Background: Silver-Russell syndrome (SRS) is a developmental disorder involving ex-treme growth failure, characteristic facial features and underlying genetic heterogeneity. As the clinical heterogeneity of SRS makes diagnosis a challenging task, the worldwide incidence of SRS could vary from 1:30,000 to 1:100,000. Although various chromosomal, genetic, and epigenetic mutations have been linked with SRS, the cause had only been identified in half of the cases. Material and Methods: To have a better understanding of the SRS clinical presentation and muta-tion/epimutation responsible for SRS, a systematic review of the literature was carried out using ap-propriate keywords in various scientific databases (PROSPERO protocol registration CRD42021273211). Clinical features of SRS have been compiled and presented corresponding to the specific genetic subtype. An attempt has been made to understand the recurrence risk and the role of model organisms in understanding the molecular mechanisms of SRS pathology, treatment, and management strategies of the affected patients through the analysis of selected literature. Results: 156 articles were selected to understand the clinical and molecular heterogeneity of SRS. Information about detailed clinical features was available for 228 patients only, and it was observed that body asymmetry and relative macrocephaly were most prevalent in cases with methylation defects of the 11p15 region. In about 38% of cases, methylation defects in ICRs or genomic muta-tions at the 11p15 region have been implicated. Maternal uniparental disomy of chromosome 7 (mUPD7) accounts for about 7% of SRS cases, and rarely, uniparental disomy of other autosomes (11, 14, 16, and 20 chromosomes) has been documented. Mutation in half of the cases is yet to be identified. Studies involving mice as experimental animals have been helpful in understanding the underlying molecular mechanism. As the clinical presentation of the syndrome varies a lot, treat-ment needs to be individualized with multidisciplinary effort. Conclusion: SRS is a clinically and genetically heterogeneous disorder, with most of the cases be-ing implicated with a mutation in the 11p15 region and maternal disomy of chromosome 7. Recur-rence risk varies according to the molecular subtype. Studies with mice as a model organism have been useful in understanding the underlying molecular mechanism leading to the characteristic clin-ical presentation of the syndrome. Management strategies often need to be individualized due to varied clinical presentations.

To evaluate the pathogenic variants in GCDH gene and to assess the neurodevelopmental outcomes in children with Glutaric aciduria type 1 (GA-1).Cross-sectional observational study between January 2019 and June 2020 in consecutive North Indian children with a clinical and biochemical suspicion of GA-1. Variants in the coding regions of GCDH gene were identified through Sanger sequencing. Neurodevelopmental and quality of life assessment was done using standardized scales.24 children with GA-1 were identified. The median age at diagnosis was 12 months and the median delay in diagnosis was 3 months. Genetic analysis was done in 14 cases. It revealed 12 variants (11 missense and one nonsense) from 13 patients. Most of the pathogenic variants were in exon 9 and exon 5. Three novel variants were identified in three patients: two missense variants c.169G A (p.Glu57Lys), c.1048TC (p.Cys350Arg) and one nonsense variant c.331CT (p.Lys111Ter). On neurodevelopmental assessment, majority of children with GA-1 were non ambulatory (62.5%), had limited hand skills (58.3%) and impaired communication (58.3%). Overall, poor global development was noted in 43.7%. A pre-existing developmental delay was significantly associated with impaired communication skills (p = 0.03), and the number of episodes of encephalopathy were significantly associated with impaired gross motor skill (p = 0.02). Presence of encephalopathy was significantly associated with poor performance in social emotional (p = 0.01) and cognitive (p = 0.03) domains of Developmental Profile-III scale and development of severe dystonia (p = 0.01).Our findings highlight the clinical, biochemical, radiological and genetic spectrum of GA-1 in children in North India and report the presence of novel pathogenic variations.

In this review, epi/genetic mutations of IGF-axis components associated with growth disorders have been summarized alongwith assessment of relevant diagnostic and therapeutic technology through patent literature.PROSPERO protocol registration CRD42021279468. For scientific literature search Literature databases (PubMed, EMBASE, ScienceDirect, and Google Scholar) were queried using the appropriate syntax. Various filters were applied based on inclusion and exclusion criteria. Search results were further refined by two authors for finalizing studies to be included in this synthesis. For patent documents search Patent databases (Patentscope and Espacenet) were queried using keywords: IGF or IGFBP. Filters were applied according to International Patent Classification (IPC) and Cooperative Patent Classification (CPC). Search results were reviewed by two authors for inclusion in the patent landscape report.For scientific literature analysis, out of 545 search results, 196 were selected for review based on the inclusion criteria. For Patent literature search, out of 485 results, 37 were selected for this synthesis.Dysregulation of IGF-axis components leads to various abnormalities and their key role in growth and development suggests epi/mutations or structural defects among IGF-axis genes can be associated with growth disorders and may explain some of the idiopathic short stature cases. Trend of patent filings indicate advent of recombinant technology for therapeutics.

Background: β-thalassemia is an autosomal recessive condition that causes a reduction in the production of haemoglobin. Despite their short lifespans, thalassemia patients must rely on routine blood transfusions throughout their lives. They suffer from a variety of health issues, the majority of which are caused by iron overload complications. It places a significant financial and psychological strain on both patients and their caregivers, and their perceived knowledge of the disease play a significant role in controlling and enhancing their health-related quality of life. Objective: To determine if caregivers of transfusion-dependent thalassemia patients are aware of thalassemia and how to manage it. Methods: The study examined the caregivers of 105 North Indian thalassemia patients who got blood transfusions on a regular basis in hospitals in Patiala, Punjab, and Chandigarh. With prior informed consent, caregivers were interviewed to evaluate their knowledge of thalassemia and its management with their socio-demographic characteristics. The knowledge of each caregiver was rated using a scoring system and was correlated to the caregiver's SES and education. The data was analysed using the SPSS version 20. Results: The majority of caregivers had sufficient knowledge about thalassemia and their comorbidities, premarital screening, treatment modalities, iron overload, and chelation therapy.

From recent years damage detection in composite structures is given a prior attention to avoid failure and breakdown of the structures. Delamination in composite structures is one of the main reasons for the failure and also affects the properties of the composite structures. Carbon fibre reinforced composite has a wide applications in industries which requires monitoring and detection of delamination for proper functioning. There are various methods such as non-destructive methods, mathematical models etc. to detect the delamination but are quiet costly, time taking and inefficient. In the present investigation, Artificial neural network (ANN) is used to determine delamination defect in carbon fiber reinforced polymer composite. ANN model can solve complex problems. Hence, the ANN model is developed to predict the delamination length and location from the fixed end by analyzing the first three carbon fiber composite structures three natural frequencies. The natural frequencies and mode shapes are obtained using finite element analysis (FEA). It has been found that the ANN can predict delamination length and location in carbon fiber reinforced polymer composite.

Use of inter-pupillary distance (IPD) for objective evaluation of ocular hypertelorism and hypotelorism is recommended to corroborate diagnosis of syndromic conditions. In view of complete absence of serial data on growth of IPD, this study aims to unfold auxological dynamics of IPD in Down syndrome (DS) children of Indian origin. Inner canthal distance (ICD) and outer canthal distance (OCD) were measured on a total of 1,125 (male: 752, female: 373) DS children, aged 0 to 3 months to 10 years at 6 monthly age intervals using a “Digimatic Sliding Caliper” in the Growth Laboratory/Growth Clinic of the Institute. Using Feingold and Bossert (1974) formula, IPD at each age was calculated from ICD and OCD measured among male and female DS children. IPD, like OCD and ICD increased un-interruptedly among DS children. IPD grew rapidly up to 5 years thereafter, its rapidity became slower. Boys in general, possessed larger IPD than girls, however, gender differences became statistically significant up to first 4 years of life. Our study children possessed significantly smaller IPD as compared with their normal Indian counterparts. None of our DS children depicted ocular hypertelorism while hypotelorism, was noticed amongst 4.9% male and 16.8% female DS patients. Comparison with normative IPD data failed to establish existence of ocular hypertelorism in DS children (

Background Short stature homeobox (SHOX) haploinsufficiency underlies idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD). The worldwide prevalence of SHOX variations in ISS varies from 2.5–15%. This study aims to assess the implication of SHOX variation in ISS in North India and its overall prevalence in Asian population. Methods SHOX gene analysis carried out by Multiplex ligation dependent probe amplification (MLPA) followed by Sanger sequencing in 54 patients with variable phenotypes. Meta-analysis was done to evaluate its prevalence which comprises 11 previous studies including present, carried out on a total of 979 participants. Results SHOX gene analysis resulted in 12.9% of positivity (7.4% deletions and 5.5% duplications). SHOX association was seen significantly related to gender, with predominance in female sex (P-value: 0.047). Short arms and forearms were the only significantly associated trait seen in 51.85% of children. We have found a rare association of multiple exostosis with LWD in a child with deletion. The prevalence of SHOX variation came as 15.2% in Asians. No significant difference was found in geographical region-specific analysis. Conclusion This meta-analysis compiles findings from the last decade and provides an updated picture of the prevalence of SHOX variations in Asians, emphasizing their potential as therapeutic targets in ISS patients.

Chromosomal aberrations/rearrangements are the most common cause of intellectual disability (ID), developmental delay (DD), and congenital malformations. Traditionally, karyotyping has been the investigation of choice in such cases, with the advantage of being cheap and easily accessible, but with the caveat of the inability to detect copy number variations of sizes less than 5 Mb. Chromosomal microarray can solve this problem, but again the problems of expense and poor availability are major challenges in developing countries. The purpose of this study is to find the utility of multiplex ligation-dependent probe amplification (MLPA) as a middle ground, in a resource-limited setting. We also attempted to establish an optimum cutoff for the de Vries score, to enable physicians to decide between these tests on a case-to-case basis, using only clinical data. A total of 332 children with DD/ID with or without facial dysmorphism and congenital malformations were studied by MLPA probe sets P245. Assessment of clinical variables concerning birth history, facial dysmorphism, congenital malformations, and family history was done. We also scored the de Vries scoring for all the patients to find a suitable cutoff for MLPA screening. In our study, the overall detection rate of MLPA was 13.5% (45/332). The majority of patients were DiGeorge's syndrome with probe deletion in 22q11.21 in 3.3% (11/332) followed by 15q11.2 del in 3.6% (12/332, split between Angelman's and Prader–Willi's syndromes). Also, 3.0% (10/332) of patients were positive for Williams–Beuren's syndrome 7q11.23, 1.8% (6/332) for Wolf–-Hirschhorn's syndrome 4p16.3, 1.2% (4/332) for 1p36 deletion, and 1% for each trichorhinophalangeal syndrome type I 8q23.3 duplication syndrome and cri du chat syndrome. The optimum cutoff of de Vries score for MLPA testing in children with ID and/or dysmorphism came out to be 2.5 (rounded off to 3) with a sensitivity of 82.2% and specificity of 66.7%. This is the largest study from India for the detection of chromosomal aberrations using MLPA common microdeletion kit P245. Our study suggests that de Vries score with a cutoff of 3 or more can be used to offer MLPA as the first tier test for patients with unexplained ID, with or without facial dysmorphism and congenital malformations.

This retrospective study was performed on 208 patients with Down syndrome (DS) from heterogeneous ethnic population and admitted under Genetics Metabolic Unit. The aim of the study was to look for phenotypic variability and associated complications in children and adolescents with DS. The average age of the evaluated DS patients was 34 months. Cardiac anomalies were found in 128 (62%) of the 208 cases. Among the cardiac disorders, atrial septal defects accounted for 30% of cases. Other complications observed were hypothyroidism and developmental delay in around 31% cases and neonatal cholestasis in 14% cases. Also, we report two cases with Moya-Moya disease and one case with atlanto-axial dislocation.

Hearing impairment is one of the most widespread inheritable sensory disorder affecting at least 1 in every 1000 born. About two-third of hereditary hearing loss (HHL) disorders are non-syndromic. To provide comprehensive update of monogenic causes of non-syndromic hearing loss (NSHL), literature search has been carried out with appropriate keywords in the following databases-PubMed, Google Scholar, Cochrane library, and Science Direct. Out of 2214 papers, 271 papers were shortlisted after applying inclusion and exclusion criterion. Data extracted from selected papers include information about gene name, identified pathogenic variants, ethnicity of the patient, age of onset, gender, title, authors' name, and year of publication. Overall, pathogenic variants in 98 different genes have been associated with NSHL. These genes have important role to play during early embryonic development in ear structure formation and hearing development. Here, we also review briefly the recent information about diagnosis and treatment approaches. Understanding pathogenic genetic variants are helpful in the management of affected and may offer targeted therapies in future.

Syndromes causing short stature include Noonan syndrome (NS), Williams syndrome, and Silver–Russell syndrome (SRS). SRS is a primordial dwarfism with genetic heterogeneity. The SRS children present with prenatal growth retardation, neonatal hypoglycemia, feeding difficulties, physical asymmetry, with scoliosis and cardiac defect in some cases. The incidence is up to 1 in 100,000. Uniparental disomy, methylation abnormalities, and variants in some genes have been found underlying such phenotype. Growth hormone therapy has been used to improve the height gain in these patients. NS has genetic heterogeneity and most patients present with short stature with or without cardiac defect. Multiple genetic variants, mostly autosomal dominant, contribute to the phenotype. With the availability of next-generation sequencing, more and more genetic disorders causing short stature are being identified in different ethnic populations like Kabuki syndrome and Nance–Horan syndrome. Here, we present some cases of SRS and other additional syndromes with dysmorphism seen in past 5 years.

Frontometaphyseal dysplasia (FMD) is a rare genetic disorder with morphological abnormalities of the skeletal and extra skeletal tissues. It belongs to the group of otopalatodigital spectrum disorders. Here we report a 12-year-old boy from India with features of frontometaphyseal dysplasia who had severe scoliosis with neurological complications due to spinal cord compromise. Clinical examination of his mother also revealed mild features of FMD. The manuscript highlights the clinical presentation of the disorder and discusses the clinical heterogeneity of the otopalatodigital spectrum disorders.

Fetal akinesia and contractures can be caused by mutations in various genes that lead to overlapping phenotypes with contractures, rocker bottom feet, cerebellar hypoplasia, ventriculomegaly, growth retardation, pulmonary hypoplasia, cystic hygroma and cleft palate in various combinations. Cerebro-oculo-facio-skeletal (COFS) syndrome is a condition resulting from defects in DNA repair pathway, and genes involved include ERCC1 (COFS), ERCC2 (XPD), ERCC5(XPG), and ERCC6 (CSB). It is a severe disorder presenting in fetal or neonatal period with microcephaly, arthrogryposis, prominent nose, and kyphoscoliosis, and leads to early death in childhood. We report a baby with antenatally identified arthrogryposis in which the homozygous pathogenic variant in exon 8 was identified in ERCC5 gene, by targeted next generation sequencing. This was predicted to cause premature chain termination in the protein. ERCC5 gene is mainly implicated in xeroderma pigmentosum, sometimes in COFS syndrome.

Wolf-Hirschhorn syndrome (WHS) (OMIM#194190) is a contiguous gene syndrome with estimated prevalence being around 1 in 50,000 births. The syndrome is caused by deletion of a critical region (Wolf-Hirschhorn Syndrome Critical region-WHSCR) on chromosome 4p16.3. Its core features are typical facial gestalt, growth retardation, intellectual disability, or developmental delay and seizures. We describe four patients, each highlighting a different aspect of this syndrome. One patient was detected by karyotype where a large deletion was identified. Three other children were diagnosed after targeted multiplex ligation-dependent probe amplification (MLPA) where heterozygous deletion of the probes on chromosome 4p16.3 were identified. One of these children additionally had heterozygous duplication of the probe for chromosome band 5p13.3. Less than half of the patients can be identified by conventional cytogenetics and molecular cytogenetic testing should be offered for diagnosis. Karyotyping of the parents should always be offered in a child with WHS.

To determine the prevalence of R501X mutation of Filaggrin gene in children with allergic diseases. Ninety patients recruited from Allergy and Asthma clinic of Advanced Pediatric Centre, PGIMER, Chandigarh and 81 healthy controls from local schools matched for age, gender and BMI were enroled in the present study. The R501X mutation analysis was done by PCR-RFLP method. Out of the 90 enroled allergic children, 5 (5.5%) were mutant (AA) for R501X genotype, 44 (43.3%) had (AA+Aa) genotype and 46 (51.1%) had (aa) genotype. However, in the control group there were no mutant (AA) for R501X, 36 (44.4%) had (AA+Aa) genotype and 45 had wild type homozygous (aa) genotype. There were 3.3% and 2.2% children with asthma and asthma concomitantly with eczema having mutant R501X genotype. In the present study, the prevalence of Filaggrin mutant genotype (R501X) was detected in approximately 5.5% of children with allergic diseases.

Cytogenetic microarray (CMA) has brought a revolution in the field of cytogenetics by improving resolution by 500 times that of traditional karyotyping. Analysis and interpretation of whole genome copy number variations (CNVs) is quite a challenging task for clinicians. Some software packages and databases are available which are based on algorithm. However, there is no clear rule to decide the pathogenicity.To formulate a step-wise approach to evaluate the interpretation of a CNV and to help the clinicians to interpret the CNV reported by a laboratory with help of four representative cases of different phenotypes.CMA was done using AffymetrixCytoscan 750K array in four cases from different families. Analysis was done based on the proposed approach.The prediction of the effect of these CNVs depends on multiple factors and can change over time as the databases are expanded. CMA in four cases from different families revealed, a rare co-occurrence of 22q13.3 duplication and 22q13.3 deletion in a proband, a deletion along with mosaicism on 10q21.2 and 10p15.3, respectively, in the second case. Third case resulted in one variant of unknown significance of 1.2 Kb deletion on 10q11.22 and the fourth case showed a benign CNV. All CNVs were analyzed based on the proposed approach and helped in subsequent management and counselling of the families. The results indicate the effectiveness of a principled, feature-based, statistical framework for uncharacterized CNV interpretation, which future studies can expand upon to construct more reliable classifiers.

The genetic influences on human growth are being increasingly deciphered. Silver–Russell and Beckwith–Wiedemann syndromes (SRS; BWS) are two relatively common genetic syndromes with under- and overgrowth-related issues being the reason for referral. Aberration in genomic imprinting is the underlying genetic pathomechanism behind these syndromes. Herein, we described a series of children with these two growth disorders and give an orientation to the reader of the concept of imprinting as well as the genetic testing strategy and counseling to be offered in these syndromes.

Osteopetrosis is a disorder characterized by high bone density, hepatosplenomegaly, visual and hearing loss, and anemia. Pycnodysostosis presents with short stature, acroosteolysis, and dense bones. We, hereby, present here a family with autosomal dominant osteopetrosis and also children with recessive osteopetrosis and pycnodysostosis. The molecular confirmation was done in 3 cases. Genetic heterogeneity in clinical presentation is discussed here. Further studies will help in identifying epigenetic alterations and population-specific variants and also developing targeted therapies.

Chromosome 1p36 deletion accounts for around 1% of cases of intellectual disability. The pattern of clinical features includes developmental delay, hypotonia, seizures, short stature, intellectual disability, vision and hearing deficits, congenital heart disease, and renal abnormalities. The size of deletion can be variable. We report four cases of 1p36 deletion syndrome detected in the past 3 years in a genetic clinic. One patient was detected by next-generation sequencing, another by chromosomal microarray, and the remaining two by multiplex ligation-dependent probe amplification. We discuss the variable presentations in the four children. Early diagnosis enables better prognostication and further reproductive planning.

Congenital deafness is one of the common disorders, with some common genes accounting for most of the cases. One in 1000 children are born with sensorineural hearing loss, and of that 50% are hereditary. In the Mediterranean Europeans, 80% of the nonsyndromic recessive deafness is due to homozygous mutation in GJB2, the 35del G allele. InWestern population, the GJB2 variation have been found in up to 30-40% cases. In Indians, the GJB2 variants have been found in up to 20% cases, mostly from central and southern India. In the present study, DNA was extracted from blood using standard methods. This was used to perform targeted gene capture using a custom capture kit. Multiple genes causing deafness were sequenced by next-generation sequencing to mean >80-100x coverage on Illumina sequencing platform. We found variants in GJB2, WFS1, FGF3, EYA4, MYO7A. and CHD7 genes. Most of these variants were pathogenic and novel, and possibly causative. Deafness is most commonly due to the autosomal dominant genes but in severe cases of early onset deafness, autosomal recessive genes may contribute in our population. In selected families of severe prelingual deafness, prenatal diagnosis can be done.

Orofaciodigital syndrome (OFD) can have variable phenotype and presents with oral anomalies, facial dysmorphism, and digital malformations like syndactyly, and polydactyly. Other presentations also include renal and cardiac defects, and central nervous system anomalies like hydrocephalus and cerebellar abnormalities. OFD1 is a X-linked dominant form of the syndrome presenting in females with mutations in CXorf5 or OFD1 gene. We describe a young child with sparse hairs, milia over face and absence of corpus callosum. Next generation sequencing showed frameshift pathogenic variant in the exon 13 of the OFD1 gene, consistent with diagnosis of OFD1.

Sotos syndrome is one of the overgrowth syndromes, and can present with intellectual disability, behavioral problems and tall stature. In some cases, seizures, pectus deformity, cardiac and renal anomalies may be identified. Here we report two Indian children with Sotos syndrome whose initial presentation was macrocephaly and behavioral problems, respectively. The pathogenic variants in NSD1 gene were confirmed by next generation sequencing. The gene variants in the two children, one male and one female; were NSD1: c.2362C>T and NSD1: c.5474dup, respectively, leading to premature termination of protein formation.

Many studies have reported the association of VEGF-1154G/A, VEGF 936C/T, and p53 Arg72Pro polymorphisms with recurrent pregnancy loss (RPL), but the outcomes are inconsistent. We have used a meta-analysis to associate these polymorphisms with RPL, having the spiral artery remodeling as a major risk factor. The studies were identified from three different reputed databases, namely ScienceDirect, PubMed/Medline, and Scopus. The eligible studies of VEGF-1154G/A, VEGF 936C/T, and p53Arg72Pro polymorphisms associated with the RPL were selected for the analysis. They were segregated into three different ethnic groups as Asians, Caucasians, and mixed population. For the analysis, the overall prevalence, odds ratio, risk ratio, relative risk ratio, and p-values were calculated. A total of 3,241 RPL cases and 3,205 healthy controls from 21 different case–control studies were analyzed. RPL was highly prevalent in the mixed population with VEGF-1154G/A and p53 Arg72Pro polymorphisms (70.04 and 66.46%, respectively) and in the Asian population with VEGF 936C/T polymorphism (53.58%). The homozygous recessive genotypes of VEGF and p53 exhibited significant association between the respective polymorphisms and RPL along with the increased risk of outcome. The current analysis conclusively reports the geographic distribution of the different genetic polymorphisms which shows high association with the progression of RPL. Understanding the spectrum of polymorphisms on different populations with the spiral artery remodeling as a risk factor encloses the importance of the vasculature during the pregnancy.

Chromosomal aberrations are an important cause of multiple malformation syndromes. Multiple ligation-dependent probe amplification (MLPA) a molecular cytogenetic technique has been suggested as a screening tool for the detection of chromosomal aberrations in resource-limited settings. MLPA can detect chromosomal microdeletions or duplications at approximately 40 chromosomal regions in a single experiment. Several MLPA kits are available to target the chromosomal regions of interest. In the present study, we aimed to detect the yield and utility of MLPA in a cohort of children with multiple malformations and developmental delay. MLPA was performed using kits P245, P070 and P036. The overall yield of MLPA in our cohort was 8%. The manuscript describes very rare and interesting cases of congenital anomalies, such as severe buphthalmos and biphalangeal fingers with a chromosomal etiology. The study demonstrates the usefulness of MLPA as screening technique for chromosomal aberrations in children with multiple malformation syndromes, especially for developing countries such as India.

The mucopolysaccharidoses (MPS) are a relatively uncommon group of inherited metabolic disorders. MPSs should be suspected in a child with coarse facies, organomegaly, recurrent respiratory tract infections, developmental delay, and hernias. Early diagnosis and treatment can greatly improve the quality of life in these children. In this study we studied 46 MPS patients diagnosed on enzyme and/or DNA testing and we found that the MPS II was the most common type followed by MPS I and MPS IVA. While the mean age of onset of symptoms was 12 months, the mean age at diagnosis was 4.5 years, a significant delay. One of major presenting features was recurrent respiratory problems, more prevalent in MPS II cases. Many patients also had short stature and contractures. Increasing awareness among physicians is of paramount importance for the early diagnosis and optimal treatment and prevention by prenatal testing and counselling.

To characterize the CYP21A2 gene mutations in children with classic congenital adrenal hyperplasia (CAH).A prospective, cross-sectional study was conducted on 24 children with classic CAH. Molecular characterization of the CYP21A2 gene was carried out by Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), or clinical exome sequencing. Another 21 previously mutation-proven CAH patients were also included and a combined result was drawn.Out of 45 children, pathogenic variants in the CYP21A2 gene were identified in 43 patients (95.5%). Homozygous, probable compound heterozygous, and heterozygous variants were seen in 69%, 22%, and 18% of patients, respectively. The most common variant was c.293-13C/AG (33%), followed by deletion/duplication (24%), and c.955CT (p.Gln319Ter) (21%), similar to previous Indian studies. Allelic frequencies of c.332_339del and c.518 TA (p.Ile173Asn) were 9% and 4%, respectively. Less common variants were c.923dupT (p.Leu308PhefsTer6), c.92CT (p.Pro31Leu), c.1069CT (p.Arg357Trp), c.1267GC (p.Gly423Arg), and c.710_719delins (p.Ile237_Met240delinsAsnGluGluLys). A good genotype-phenotype correlation was observed; only p.Pro31Leu and p.Ile173Asn variants showed discordance. The diagnostic yield of Sanger sequencing alone, Sanger sequencing with MLPA, and clinical exome alone was 85%, 100%, and 100%, respectively.All children, except two, diagnosed clinically as classic CAH, showed pathogenic variants in the CYP21A2 gene; the most common variant was c.293-13 C/AG. The results suggest a broad mutation spectrum in the authors' single-center cohort of children with CAH. Clinical exome sequencing is the preferred stand-alone method for molecular diagnosis of CAH.