Publications by authors named "Abdul Mueed Bidchol"

9 Publications

  • Page 1 of 1

Phenotype and genotype in patients with Larsen syndrome: clinical homogeneity and allelic heterogeneity in seven patients.

BMC Med Genet 2016 Apr 6;17:27. Epub 2016 Apr 6.

Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.

Background: Larsen syndrome is an autosomal dominant skeletal dysplasia characterized by large joint dislocations and craniofacial dysmorphism. It is caused by missense or small in-frame deletions in the FLNB gene. To further characterize the phenotype and the mutation spectrum of this condition, we investigated seven probands, five sporadic individuals and a mother-son-duo with Larsen syndrome.

Methods: The seven patients from six unrelated families were clinically and radiologically evaluated. All patients were screened for mutations in selected exons and exon-intron boundaries of the FLNB gene by Sanger sequencing. FLNB transcript analysis was carried out in one patient to analyse the effect of the sequence variant on pre-mRNA splicing.

Results: All patients exhibited typical facial features and joint dislocations. Contrary to the widely described advanced carpal ossification, we noted delay in two patients. We identified the five novel mutations c.4927G  A/p.(Gly1643Ser), c.4876G > T / p.(Gly1626Trp), c.4664G > A / p.(Gly1555Asp), c.2055G > C / p.Gln685delins10 and c.5021C > T / p.(Ala1674Val) as well as a frequently observed mutation in Larsen syndrome [c.5164G > A/p.(Gly1722Ser)] in the hotspot regions. FLNB transcript analysis of the c.2055G > C variant revealed insertion of 27 bp intronic sequence between exon 13 and 14 which gives rise to in-frame deletion of glutamine 685 and insertion of ten novel amino acid residues (p.Gln685delins10).

Conclusions: All seven individuals with Larsen syndrome had a uniform clinical phenotype except for delayed carpal ossification in two of them. Our study reveals five novel FLNB mutations and confirms immunoglobulin-like (Ig) repeats 14 and 15 as major hotspot regions. The p.Gln685delins10 mutation is the first Larsen syndrome-associated alteration located in Ig repeat 5. All mutations reported so far leave the filamin B protein intact in accordance with a gain-of-function effect. Our findings underscore the characteristic clinical picture of FLNB-associated Larsen syndrome and add Ig repeat 5 to the filamin B domains affected by the clustered mutations.
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http://dx.doi.org/10.1186/s12881-016-0290-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822278PMC
April 2016

Recurrent and novel GLB1 mutations in India.

Gene 2015 Aug 30;567(2):173-81. Epub 2015 Apr 30.

Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India. Electronic address:

GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in the GLB1 gene, leading to the deficiency of the enzyme β-d-galactosidase. In this study, we report molecular findings in 50 Asian Indian families with GM1 gangliosidosis. We sequenced all the exons and flanking intronic sequences of GLB1 gene. We identified 33 different mutations (20 novel and 13 previously reported). The novel mutations include 12 missense (p.M1?, p.E129Q, p.G134R, p.L236P, p.G262E, p.L297F, p.Y331C, p.G414V, p.K493N, p.L514P, p.P597L, p.T600I), four splicing (c.246-2A>G, c.397-2A>G, c.552+1G>T, c.956-2A>G), three indels (p.R22Qfs*8, p.L24Cfs*47, p.I489Qfs*4) and one nonsense mutation (p.Q452*). Most common mutations identified in this study were c.75+2InsT (14%) and p.L337P (10%). Known mutations accounted for 67% of allele frequency in our cohort of patients, suggesting that these mutations in GLB1 are recurrent across different populations. Twenty three mutations were localized in the TIM barrel domain, β-domain 1 and β-domain 2. In silico sequence and structure analysis of GLB1 reveal that all the novel mutations affect the function and structure of the protein. We hereby report on the largest series of patients with GM1 gangliosidosis and the first from India.
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http://dx.doi.org/10.1016/j.gene.2015.04.078DOI Listing
August 2015

White matter changes in GM1 gangliosidosis.

Indian Pediatr 2015 Feb;52(2):155-6

Departments of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh; and *Kasturba Medical College, Manipal University, Manipal, India. Correspondence to: Dr Shubha R Phadke, Professor and Head, Department of Medical Genetics, SGPGIMS, Lucknow 226 014.

Background: GM1 gangliosidosis is a disorder due to GLB1 gene mutation.

Case Characteristics: A 4-yr-old boy with neuroregression and optic atrophy with periventricular hyperintensity on magnetic resonance imaging.

Outcome: Beta galactosidase enzyme activity was low which was confirmed by GLB1 sequencing.

Message: We highlight the white matter changes in late infantile GM1 gangliosidosis.
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http://dx.doi.org/10.1007/s13312-015-0593-2DOI Listing
February 2015

Exome Sequencing Identifies a Dominant TNNT3 Mutation in a Large Family with Distal Arthrogryposis.

Mol Syndromol 2014 Aug 8;5(5):218-28. Epub 2014 Jul 8.

Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India.

Distal arthrogryposis (DA) is a group of rare, clinically and genetically heterogeneous disorders primarily characterized by congenital contractures of the distal limb joints without a neuromuscular disease. Mutations in at least 8 different genes have been shown to cause DA. Here, we report a 4-generation Indian family with 18 affected members presenting variable features of camptodactyly, brachydactyly, syndactyly, decreased flexion palmar creases, ulnar deviation of the hands, sandal gaps and club feet. We undertook exome sequencing of 3 distantly related affected individuals. Bioinformatics filtering revealed a known pathogenic missense mutation c.188G>A (p.Arg63His) in TNNT3 in all 3 affected individuals that segregated with the phenotype. The affected individuals exhibit significant phenotypic variability. This study demonstrates the value of exome sequencing helping to define the causative variant in genetically heterogeneous disorders.
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http://dx.doi.org/10.1159/000365057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188168PMC
August 2014

GALNS mutations in Indian patients with mucopolysaccharidosis IVA.

Am J Med Genet A 2014 Nov 22;164A(11):2793-801. Epub 2014 Sep 22.

Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India.

Mucopolysaccharidosis IV A (Morquio syndrome A, MPS IVA) is a lysosomal storage disease caused by the deficiency of N-acetylgalactosamine-6-sulfatase (GALNS). The mutation spectrum in this condition is yet to be determined in Indians. We aimed to analyze the mutations in the GALNS gene in Asian Indians with MPS IVA. All the exons and the adjacent intronic regions of the gene were amplified and sequenced in sixty-eight unrelated Indian families. We identified 136 mutant alleles comprising of 40 different mutations. We report twenty-two novel mutations that comprise of seventeen missense (p.Asn32Thr, p.Leu36Arg, p.Pro52Leu, p.Pro77Ser, p.Cys79Arg, p.His142Pro, p.Tyr191Asp, p.Asn204Thr, p.Gly188Ser, p.Phe216Ser, p.Trp230Cys, p.Ala291Ser, p.Gly317Arg, p.His329Pro, p.Arg386Ser, p.Glu450Gly, p.Cys501Ser), three splice-site variants (c.120+1G>C, c.1003-3C>G, c.1139+1G>A), one nonsense mutation (p.Gln414*) and one frameshift mutation (p.Pro420Leufs*440). Eighteen mutations have been reported earlier. Among these p.Ser287Leu (8.82%), p.Phe216Ser (7.35%), p.Asn32Thr (6.61%) and p.Ala291Ser (5.88%) were the most frequent mutations in Indian patients but were rare in the mutational profiles reported in other populations. These results indicate that the Indian patients may have a distinct mutation spectrum compared to those of other populations. Mutant alleles in exon 1, 7 and 8 accounted for 44.8% of the mutations, and sequencing of these exons initially may be a cost-effective approach in Asian Indian patients. This is the largest study on molecular analysis of patients with MPS IVA reported in the literature, and the first report from India.
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http://dx.doi.org/10.1002/ajmg.a.36735DOI Listing
November 2014

A novel mutation (g.106737G>T) in zone of polarizing activity regulatory sequence (ZRS) causes variable limb phenotypes in Werner mesomelia.

Am J Med Genet A 2014 Apr 29;164A(4):898-906. Epub 2014 Jan 29.

Division of Medical Genetics, Department of Pediatrics, Kasturba Medical College, Manipal University, Manipal, India.

Werner mesomelia is characterized by a sequence variation in the specific region (position 404) of the enhancer ZRS of SHH. The phenotype comprises variable mesomelia, abnormalities of the thumb and great toe and supernumerary digits. We describe extensive variation in limb phenotype in a large family and report on a novel sequence variation NG_009240.1: g.106737G>T (traditional nomenclature: ZRS404G>T) in the ZRS within the LMBR1 gene. The newly recognized clinical features in this family include small thenar eminence, sandal gap, broad first metatarsals, mesoaxial polydactyly, and postaxial polydactyly. We provide information on 12 affected family members. We review the literature on how a sequence variation in ZRS may cause such diverse phenotypes.
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http://dx.doi.org/10.1002/ajmg.a.36367DOI Listing
April 2014

A novel frameshift mutation in TWIST2 gene causing Setleis syndrome.

Indian J Pediatr 2014 Mar 15;81(3):302-4. Epub 2013 Oct 15.

Division of Medical Genetics, Department of Pediatrics, Kasturba Medical College, Manipal University, Manipal, 576104, India,

The authors report on a child with Setleis syndrome (OMIM 227260). She is born to a consanguineous couple with bitemporal scar like defects resembling forceps marks. She had other classical features resembling autosomal recessive Setleis syndrome. The authors identified a novel homozygous deletion of a single nucleotide (c.91delC) in TWIST2 gene leading to the premature truncation of protein (p.R31GfsX71). Umbilical hernia and genital anomalies are being reported for the first time with this condition. This is the fourth mutation proven family of Setleis syndrome.
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http://dx.doi.org/10.1007/s12098-013-1253-yDOI Listing
March 2014

Novel mutation in an Indian patient with Methylmalonic Acidemia, cblA type.

Indian J Hum Genet 2012 Sep;18(3):346-8

Department of Pediatrics, Kasturba Medical College, Manipal University, Manipal, India.

We report on a girl with methylmalonic acidemia, cblA type with a novel homozygous mutation and describe the clinical phenotype and response to therapy.
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http://dx.doi.org/10.4103/0971-6866.108025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656526PMC
September 2012

Analysis of the WISP3 gene in Indian families with progressive pseudorheumatoid dysplasia.

Am J Med Genet A 2012 Nov 17;158A(11):2820-8. Epub 2012 Sep 17.

Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Andhra Pradesh, India.

Progressive pseudorheumatoid dysplasia (PPD) is a progressive skeletal syndrome characterized by stiffness, swelling and pain in multiple joints with associated osteoporosis in affected patients. Radiographically, the predominant features resemble a spondyloepiphyseal dysplasia. Mutations in the WISP3 gene are known to cause this autosomal recessive condition. To date, only a limited number of studies have looked into the spectrum of mutations causing PPD. We report on clinical features and WISP3 mutations in a large series of Indian patients with this rare skeletal dysplasia. Families with at least one member showing clinical and radiologic features of PPD were recruited for the study. Symptoms, signs and radiographic findings were documented in 35 patients from 25 unrelated families. Swelling of small joints of hands and contractures are the most common presenting features. Mutation analysis was carried out by bidirectional sequencing of the WISP3 gene in all 35 patients. We summarize the clinical features of 35 patients with PPD and report on 11 different homozygous mutations and one instance of compound heterozygosity. Eight (c.233G>A, c.340T>C, c.348C>A, c.433T>C, c.682T>C, c.802T>G, c.947_951delAATTT, and c.1010G>A) are novel mutations and three (c.156C>A, c.248G>A, and c.739_740delTG) have been reported previously. One missense mutation (c.1010G>A; p.Cys337Tyr) appears to be the most common in our population being seen in 10 unrelated families. This is the largest cohort of patients with PPD in the literature and the first report from India on mutation analysis of WISP3. We also review all the mutations reported in WISP3 till date.
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http://dx.doi.org/10.1002/ajmg.a.35620DOI Listing
November 2012