Publications by authors named "Tanushree Chawla"

6 Publications

  • Page 1 of 1

Comparison of The Carrier Frequency of Pathogenic Variants of DMD Gene in an Indian Cohort.

J Neuromuscul Dis 2021 Apr 2. Epub 2021 Apr 2.

Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India.

Background: Duchenne muscular dystrophy (DMD) is an X-linked disorder caused due to large deletions, duplications,and small pathogenic variants. This article compares the carrier frequency of different pathogenic variants in the DMD gene for the first time in an Indian cohort.

Methods: Ninety-one mothers of genetically confirmed DMD probands are included in this study. Pathogenic variants in the DMD gene in probands were detected by multiplex ligation-dependent probe amplification (MLPA) or next-generation sequencing (NGS). Maternal blood samples were evaluated either by MLPA or Sanger sequencing. The demographic and clinical details for screening of muscle weakness and cardiomyopathy were collected from the confirmed carriers.

Results: Out of 91 probands, large deletions and duplications were identified in 46 and 6 respectively, while 39 had small variants. Among the small variants, substitutions predicted to cause nonsense mutations were the most common (61.5%), followed by frameshift causing small insertion/deletions (25.6%) and splice affecting intronic variants (12.8%). Notably, 19 novel small variants predicted to be disease-causing were identified. Of the 91 mothers, 53 (58.7%) were confirmed to be carriers. Exonic deletions had a significantly lower carrier frequency of 47.8% as compared to small variants (64.1%). The mean age of the carriers at evaluation was 30 years. Among the carriers, two were symptomatic with onset in the 4th decade, manifesting with progressive proximal muscle weakness and dilated cardiomyopathy.

Conclusion: Carrier frequency of small pathogenic variants differs significantly from large deletions. Small pathogenic variants are more commonly inherited, whereas large deletions arise de novo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JND-210658DOI Listing
April 2021

Megaconial congenital muscular dystrophy secondary to novel CHKB mutations resemble atypical Rett syndrome.

J Hum Genet 2021 Mar 12. Epub 2021 Mar 12.

Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India.

Megaconial congenital muscular dystrophy (CMD)(OMIM #602541), related to CHKB mutation, is a rare autosomal recessive disorder. To date, only 35 confirmed patients are recorded. We present a detailed description of the clinical, histopathological, imaging, and genetic findings of five children from four Indian families. The children had moderate-to-severe autistic behavior, hand stereotypies, and global developmental delay mimicking atypical Rett syndrome. In addition, generalized hypotonia was a common initial finding. The progression of muscle weakness was variable, with two patients having a milder phenotype and three having a severe form. Interestingly, the majority did not attain sphincter control. Only patient 1 had classical ichthyotic skin changes. Muscle biopsy in two patients showed a myopathic pattern with characteristic peripherally placed enlarged mitochondria on modified Gomori trichrome stain and electron microscopy. Genetic analysis in these patients identified three novel null mutations in CHKB [c.1027dupA (p.Ser343LysfsTer86);c.224 + 1G > T (5' splice site); c.1123C > T (p.Gln375Ter)] and one reported missense mutation, c.581G > A (p.Arg194Gln), all in the homozygous state. Megaconial CMD, although rare, forms an important group with a complex phenotypic presentation and accounted for 5.5% of our genetically confirmed CMD patients. Atypical Rett syndrome-like presentation may be a clue towards CHKB-related disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s10038-021-00913-1DOI Listing
March 2021

Recessive VAMP1 mutations associated with severe congenital myasthenic syndromes - A recognizable clinical phenotype.

Eur J Paediatr Neurol 2021 Mar 16;31:54-60. Epub 2021 Feb 16.

Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India. Electronic address:

Three unrelated girls, all born to consanguineous parents had respiratory distress, severe hypotonia at birth along with prominent fatigable muscle weakness and characteristic myopathic facies. In addition, patient 1 had fatigable ptosis, ophthalmoparesis and profound bulbar weakness and required nasogastric feeding from birth. A feeding gastrostomy was inserted at 9 months of age. She continued to have severe bulbar and limb weakness with dropped head at 5 years of age. Patient 2 and 3 did not have ocular signs at the time of initial presentation during infancy and at 2 years of age respectively. None of the patients attained independent walking. Patient 3, currently aged 16 years continues to be wheelchair bound and has only mild non-progressive bulbar weakness with normal cognitive development. Muscle biopsy in patient 1 and 3 showed predominant myopathic features admixed with small sized (atrophic/hypoplastic) fibres. Next generation sequencing confirmed the presence of a homozygous loss of function VAMP1 mutations in all three patients: A single nucleotide deletion resulting in frameshift: c.66delT (p.Gly23AlafsTer6) in patient 1 and nonsense mutations c.202C>T (pArg68Ter) and c.97C>T (p.Arg33Ter) in patient 2 and 3 respectively. Minimal but definite improvement in muscle power with pyridostigmine was reported in patients 1 and 2. This is the first report of VAMP1 mutations causing CMS from the Indian subcontinent, describing a clinically recognizable severe form of VAMP1-related CMS and highlighting the need for a strong index of suspicion for early genetic diagnosis of potentially treatable CMS phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpn.2021.02.005DOI Listing
March 2021

Altered REM sleep architecture in patients with Myotonic dystrophy type 1: is related to sleep apnea?

Sleep Med 2021 Mar 1;79:48-54. Epub 2021 Jan 1.

Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India. Electronic address:

Objective: To determine the sleep architecture and sleep respiratory abnormalities and to correlate with sleep symptoms in patients with Myotonic dystrophy type 1 (DM1).

Methods: We recruited a cohort of genetically confirmed patients with DM1, who attended the Neuromuscular clinic between July 2016 and December 2019. Clinical, sleep and whole night polysomnography data were collected. The analysis of sleep architecture, sleep respiratory parameters and comparison with healthy controls (HC) was performed in our sleep laboratory.

Results: A total of 59 patients with DM1 underwent sleep evaluation. Hypersomnolence in 42 (77.8%), ESS>10 in 23 (39%), and PSQI>5 in 18 (30.5%) were found in patients with DM1. Thirty-one (68.89%) patients with DM1 and 22 (95.65%) HC had more than 4-h of total sleep time (TST). More than 4 h of TST was taken to compare respiratory and sleep architecture parameters. Patients with DM1 had reduced sleep efficiency, reduced N2 sleep, and increase in N1 sleep, wake index, stage shift index, nocturnal sleep-onset REM periods compared to HC. AHI>15 was found in 16 (51.61%) DM1 and in 3 HC (13.64%). AHI had positive correlation with BMI, but not with age, ESS or disease progression (MIRS). All DM1 with AHI>15; 8(80%) and 1(33.33%) in AHI5to15, and AHI<5 groups, respectively had hypersomnolence.

Conclusion: In this first study on Indian cohort, daytime hypersomnolence, poor nocturnal sleep quality, sleep architecture irregularities are identified to be common in patients with DM1. These abnormalities may be explained by sleep-related breathing disorders that are highly prevalent in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sleep.2020.12.036DOI Listing
March 2021

Young Male with Paraparesis and Vision Loss- A Rare Presentation of Eales' Disease.

Ann Indian Acad Neurol 2020 Jul-Aug;23(4):563-566. Epub 2020 Jun 29.

Department of Neurology, Govind Ballabh Pant Institute of Post Graduate Medical Education and Research (GIPMER), New Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/aian.AIAN_573_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657282PMC
June 2020