Pulmonary manifestations in hyper IgE syndrome: A case series and review of Indian literature.

Recurrent pulmonary infections starting from childhood often prompt evaluation for primary immunodeficiency disorders (PIDs). Hyper IgE syndrome (HIES) is a less common PID characterised by recurrent skin and pulmonary infections associated with elevated IgE levels. Staphylococcal infections are more commonly seen in these individuals, resulting in structural lung abnormalities such as pneumatoceles and bronchiectasis.

Functional Characterization of Thyroid Peroxidase Missense Variants Causing Thyroid Dyshormonogenesis in Asian Indian Population.

Introduction: Thyroid dyshormonogenesis (TDH) is a subgroup of congenital hypothyroidism with recessive inheritance resulting from disease-causing variants in thyroid hormone biosynthesis pathway genes, like DUOX2, TG, TPO, SLC5A5, SLC26A4, IYD, DUOXA2, and SLC26A7. Thyroid peroxidase (TPO) is a crucial enzyme involved in thyroid hormone biosynthesis and is one of the frequently mutated genes in patients with TDH. The purpose of the study was to describe the in silico and functional characterization of novel variants in TPO gene identified in patients with TDH.

Short stature and dysmorphic features in Asian Indian siblings with DAAM2-associated steroid-resistant nephrotic syndrome: Expansion of the phenotypic spectrum or a blended phenotype?

Variants in more than 60 different genes, most of which code for podocyte-related proteins, have been found to be associated with monogenic forms of nephrotic syndrome (NS). Biallelic variants in DAAM2, a member of the formin family, were recently identified to cause autosomal recessive (AR) NS type 24 in four unrelated families with steroid-resistant nephrotic syndrome (SRNS). This case report represents only the fifth reported family of DAAM2-associated NS and the first from India, with two sibs who presented with a complex phenotype characterized by steroid-resistant nephrotic syndrome, short stature, dysmorphic facial features, deep-set toenails, myopia, increased thickness of the calvarium of the skull, and sloping ribs.

Etiologic Spectrum of Pediatric-Onset Leukodystrophies and Genetic Leukoencephalopathies: The Five-Year Experience of a Tertiary Care Center in Southern India.

Background: White matter (WM) disorders with a genetic etiology are classified as leukodystrophies (LDs) and genetic leukoencephalopathies (GLEs). There are very few studies pertaining to the etiologic spectrum of these disorders in the Asian Indian population.

Methods: This study was conducted over a period of five years from January 2016 to December 2020, in the medical genetics department of a tertiary care hospital in southern India.

Long-range PCR amplification-based targeted enrichment & next generation sequencing: A cost-effective testing strategy for lysosomal storage disorders.

Background & Objectives: Lysosomal storage disorders (LSDs) are genetic metabolic disorders which result from deficiency of lysosomal enzymes or defects in other lysosomal components. Molecular genetic testing of LSDs is required for diagnostic confirmation when lysosomal enzyme assays are not available or not feasible to perform, and for the identification of the disease causing genetic variants. The aim of this study was to develop a cost-effective, readily customizable and scalable molecular genetic testing strategy for LSDs.

A novel homozygous synonymous splicing variant in SELENOI gene causes spastic paraplegia 81.

Background: Hereditary spastic paraplegia 81 is a recently identified, rare autosomal recessive disease, caused by biallelic pathogenic variants in the SELENOI gene, with only two families reported to date. The features documented in the two previous affected families include sensorineural deafness, blindness, cleft palate, delayed motor development, regression of motor skills, impaired intellectual development, poor speech and language acquisition, spasticity, hyperreflexia, white matter abnormalities and cerebral and cerebellar atrophy.

Methods: In the present study, we performed exome sequencing analysis in a single family with two affected siblings to identify the genetic cause of complicated hereditary spastic paraplegia.

Consensus Statement of the Neurodevelopmental Pediatrics Chapter of Indian Academy of Pediatrics (IAP) on the Management of Children With Down Syndrome.

Justification: The diagnosis of Down syndrome (DS) is easily made clinically but the management is multi-disciplinary and life-long. There is no standard protocol available for its management in India.

Process: A committee was formed under the Indian Academy of Pediatrics (IAP) chapter of Neuro developmental pediatrics consisting of 20 experts working in the related field.

Proband only exome sequencing in 403 Indian children with neurodevelopmental disorders: Diagnostic yield, utility and challenges in a resource-limited setting.

Whole exome sequencing is recommended as the first tier test for neurodevelopmental disorders (NDDs) with trio being an ideal option for the detection of de novo variants. Cost constraints have led to adoption of sequential testing i.e.

Genetic Evaluation of the Parents Following Demise of the Index Case: Report of a Family with Fucosidosis.

It is common in obstetric practice to encounter couples who seek prenatal genetic counseling and testing in view of history of known or suspected genetic disorders in the previous offspring or in other family members. Recent advances in genetic testing techniques, especially the availability of the next-generation sequencing (NGS) technology, have greatly facilitated genetic evaluation of the proband and/or the consultand couple and enabled provision of accurate genetic counseling and prenatal genetic testing in such clinical scenarios. However, even in this era of NGS, comprehensive clinical history taking and detailed phenotype characterization through clinical examination and thorough perusal of available medical records, are very important and essential for accurate diagnosis, as reiterated by this report of a 30-year-old third gravida, who was referred for prenatal genetic counseling and testing, in view of history of death of the first offspring due to a suspected neurogenetic disorder.

Clinical and Molecular Spectrum of Degenerative Cerebellar Ataxia: A Single Centre Study.

Background: Cerebellar ataxia is a disabling neurological symptom with extreme clinical and etiological heterogeneity.

Objective: To study the clinical and molecular characteristics in patients with degenerative cerebellar ataxia.

Materials And Methods: In this study, 150 South-Indian patients with degenerative cerebellar ataxia underwent a phenotype guided, sequential tiered testing.

Genetics and muscle pathology in the diagnosis of muscular dystrophies: An update.

Muscular dystrophies are a clinically and genetically heterogeneous group of disorders involving the skeletal muscles. They have a progressive clinical course and are characterized by muscle fiber degeneration. Congenital muscular dystrophies (CMD) include dystroglycanopathies, merosin-deficient CMD, collagen VI-deficient CMD, SELENON-related rigid spine muscular dystrophy, and LMNA-related CMD.

Genotype-phenotype spectrum of 130 unrelated Indian families with Mucopolysaccharidosis type II.

MPS II is an X linked recessive lysosomal storage disorder with multi-system involvement and marked molecular heterogeneity. In this study, we explored the clinical and molecular spectrum of 144 Indian patients with MPS II from 130 unrelated families. Clinical information was collected on a predesigned clinical proforma.

Ectodysplasin pathogenic variants affecting the furin-cleavage site and unusual clinical features define X-linked hypohidrotic ectodermal dysplasia in India.

Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disorder caused by mutational inactivation of a developmental pathway responsible for generation of tissues of ectodermal origin. The X-linked form accounts for the majority of HED cases and is caused by Ectodysplasin (EDA) pathogenic variants. We performed a combined analysis of 29 X-linked hypohidrotic ectodermal dysplasia (XLHED) families (including 12 from our previous studies).

Approach to inherited hypertrichosis: A brief review.

Hypertrichosis refers to the growth of hair, of an excessive amount and thickness, on any part of the body. It must be distinguished from hirsutism which is characterized by excess growth of hair in androgen-dependent areas on the upper lip, chin, chest, linea alba, thigh and axilla. Hypertrichosis may be localized or generalized, and congenital or acquired.

Functional characterization of novel variants in SMPD1 in Indian patients with acid sphingomyelinase deficiency.

Pathogenic variations in SMPD1 lead to acid sphingomyelinase deficiency (ASMD), that is, Niemann-Pick disease (NPD) type A and B (NPA, NPB), which is a recessive lysosomal storage disease. The knowledge of variant spectrum in Indian patients is crucial for early and accurate NPD diagnosis and genetic counseling of families. In this study, we recruited 40 unrelated pediatric patients manifesting symptoms of ASMD and subnormal ASM enzyme activity.

Phenotypic and genotypic spectrum of CTSK variants in a cohort of twenty-five Indian patients with pycnodysostosis.

Background: Pycnodysostosis is an autosomal recessive skeletal dysplasia with easily recognizable clinical features and marked molecular heterogeneity. In this study, we explored the clinical and molecular spectrum of 25 Indian patients with pycnodysostosis from 20 families.

Methods: Clinical information was collected on a predesigned clinical proforma.

Eye of the Tiger: Looking Beyond Neurodegeneration with Brain Iron Accumulation Disorders.

The "eye-of-the-tiger" sign in brain magnetic resonance imaging (MRI) is typically associated with neurodegeneration with brain iron accumulation disorders, especially pantothenate kinase-associated neurodegeneration. However, very similar neuroimaging findings may be seen in other neurodegenerative disorders involving the basal ganglia. We report here a patient with fucosidosis who had MRI brain findings closely resembling the "eye-of-the-tiger" sign.

Next-Generation Sequencing in a Cohort of Asian Indian Patients with the Duchenne Muscular Dystrophy Phenotype: Diagnostic Yield and Mutation Spectrum.

Multiplex ligation-dependent probe amplification (MLPA) detects exonic deletions and duplications in the gene in around 65 to 70% of patients with the Duchenne muscular dystrophy (DMD) phenotype. This study looks at the diagnostic yield of next-generation sequencing (NGS) and the mutation spectrum in an Asian Indian cohort of MLPA-negative cases with the DMD phenotype. NGS-based sequencing of gene was done in 28 MLPA-negative cases (25 male probands with the DMD phenotype and 3 obligate carrier mothers of deceased affected male patients) and disease-causing variants were identified in 19 (67.

Fabry disease in India: A multicenter study of the clinical and mutation spectrum in 54 patients.

Fabry disease (FD) is a treatable X linked lysosomal storage disorder with a wide phenotypic spectrum. There is a scarcity of published data on the burden of FD in India. This study evaluates the clinical and molecular spectrum of Indian patients with FD.

Identification and characterization of 30 novel pathogenic variations in 69 unrelated Indian patients with Mucolipidosis Type II and Type III.

Mucolipidosis (ML) (OMIM 607840 & 607838) is a rare autosomal recessive inherited disorder that occurs due to the deficiency of golgi enzyme uridine diphosphate (UDP)- N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) responsible for tagging mannose-6-phosphate for proper trafficking of lysosomal enzymes to lysosomes. Variants in GlcNAc-phosphotransferase (GNPTAB (α, β subunits) and GNPTG (γ subunits) are known to result in impaired targeting of lysosomal enzymes leading to Mucolipidosis (ML) Type II or Type III. We analyzed 69 Indian families of MLII/III for clinical features and molecular spectrum and performed in silico analysis for novel variants.

A newly recognized multiple malformation syndrome with caudal regression associated with a biallelic c.402G>A variant in TBX4.

The T-box4 (TBX4) gene (OMIM *601719) belongs to the T-box family of transcription regulators that share a conserved homology domain and are expressed at specific sites during various stages of embryonic development. Tbx4 has been found to be a crucial transcriptional regulator in embryonic hindlimb development in animal models. Monoallelic variants in the TBX4 gene are reported to be associated with skeletal defects of the pelvis and lower limbs.