Cutaneous mastocytosis. Getting beneath the skin of the issue: a case report

An eleven month old girl presented with chronic urticaria since three months of age. There was a generalised hyperpigmented maculo-papular rash. Darier sign was positive. The skin biopsy showed plenty of spindle shaped mast cells with eosinophilic cytoplasm infiltrating the dermis and the appendiceal structures. The diagnosis of cutaneous mastocytosis (urticaria pigmentosa) was made. The child received symptomatic relief with chronic oral hydroxyzine and ranitidine therapy. Automated epinephrine self-injectors usually prescribed in this condition for self-management of anaphylactic episodes were not available. Intramuscular administration of (1:1000) diluted adrenaline via a disposable tuberculin syringe was taught to the mother. A medical bracelet containing her diagnosis and instructions in emergency was custom-made for her

Clinical profile and molecular diagnosis in patients of facioscapulohumeral dystrophy from Indian subcontinent

Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant muscular dystrophy. We retrospectively studied three families (two Indian, one Nepalese) with 12 affected members (male:female-7:5). Mean age at onset of weakness was 17.63 + 5.48 years. Patients were classified according to muscle groups affected (F-face, S-scapula, H-humeral, PG-pelvic girdle, P-peroneal, A-loss of independent ambulation): FSH-A (2), four FSH (4), SH (3), FSH-PG (2) and one: F (1). Progression of weakness was classified as F>S>P>PG in eight cases, S> F>P in one, static in three. Eleven patients had electromyographic findings suggestive of myopathy and one had features of neurogenic involvement. Molecular diagnosis was done by southern blotting using probe p13E-ni11 after digestion of genomic DNA with EcoRI and/or EcoRI/BlnI for twelve patients and three unaffected relatives. No EcoRI fragment smaller than 35 Kb was seen in unaffected subjects. Size of EcoRI fragment varied between 17 kb to 27 kb in affected subjects and was constant for affected members of the same family. Molecular diagnosis by southern blotting has helped to provide genetic counseling for the families

GRIN1- Related neurodevelopmental disorder-Autism with Epilepsy - A case report

<p>GRIN1-related neurodevelopmental disorders are  a group of rare paediatric encephalopathies,with  estimated    prevalence    of    1:5000    births     (1) .Genetic variation in the GRIN1 gene have been  associated with a wide range of neurologic and  neuropsychiatric  disorders  .GRIN1  (Glutamate  Receptor   Inotropic,   NMDA   1)   is   the   name  of  the  gene  that  is  affected.</p&gt

Mutation analysis of mitogen activated protein kinase 1 gene in Indian cases of 46,XY disorder of sex development

Background: Determination of sex is the result of cascade of molecular events that cause undifferentiated bipotential gonad to develop as a testis or an ovary. A series of genes such as SRY, steroidogenic factor-1 (SF1), AR, SRD5 α, Desert hedgehog (DHH) etc., have been reported to have a significant role in development of sex in the fetus and secondary sexual characteristics at the time of puberty. Recently, mitogen activated protein kinase kinase kinase 1 (MAP3K1) gene was found to be associated with 46, XY disorders of sex development (DSD). Aim: The present study is focused to identify mutations in MAP3K1 gene in the cohort of 10 Indian patients with 46,XY DSD including one family with two affected sisters. These patients were already screened for SRY, SF1 and DHH gene, but no mutation was observed in any of these genes. Materials and Methods: The entire coding regions of MAP3K1 were amplified and sequenced using the gene specific primers. Results and Discussions: Sequence analysis of MAP3K1 gene has revealed four variants including one missense, two silent and one deletion mutation. The missense mutation p.D806N was observed in four patients with hypospadias. Two patients showed the presence of silent mutation p.Q1028Q present in exon 14. Another silent mutation p.T428T was observed in a patient with gonadal dysgenesis. We have also observed one deletion mutation p. 942insT present in two patients. The pathogenicity of the missense mutation p.D806N was carried out using in-silico approach. Sequence homology analysis has revealed that the aspartate at 806 was found to be well-conserved across species, indicated the importance of this residue. The score for polyphen analysis of this mutation was found to be 0.999 indicating to be pathogenic mutation. Since, p.D806N mutation was found to be important residue; it might contribute to sexual development. We have reported the presence of mutations/polymorphism in MAP3K1 gene. All the mutations were found to be polymorphism upon comparing to single nucleotide polymorphism database. However, in-silico analysis of the missense mutation revealed to be a pathogenic mutation

Prevention of homozygous beta thalassemia by premarital screening and prenatal diagnosis in India

Aim: To determine the feasibility and acceptability of premarital screening for beta thalassemia/related hemoglobinopathies followed by prenatal diagnosis in India. Materials and Methods: Premarital testing for thalassemia carrier state was carried out in (1) extended family members (EFM) of diagnosed cases of thalassemia/hemoglobinopathies, (2) unmarried adult cases of anemia attending the hospitals' outpatient department (OPD) and (3) adult college students (CG). Hemoglobin, red cell indices were measured by a cell counter and hemoglobin fractionation was carried out by high performance liquid chromatography (HPLC). In cases with HbA2 > 3.5%, or with variant hemoglobin, mutation screen was done by amplification refractory mutation system polymerase chain reaction (ARMS- PCR). In high-risk prospective couples, premarital genetic counseling was done and prenatal diagnosis possibilities were explained. Results: The yield of carriers from EFM, OPD and CG groups was 78.17% (308/394), 19.51% (263/1348) and 4.04% (38/939), respectively. The number of prospective high-risk couples detected were 154, 48 and 2 from EFM, OPD and CG, respectively. As much as 99% of prospective carrier couples married even after knowing their high-risk status and opted for prenatal diagnosis. The program averted the birth of 33 thalassemic children; 28 in EFM group (by screening of 394 individuals), 4 in the OPD group (by screening 1348 anemic patients), and 1 in CG group (by screening of 939 students). Conclusion: Premarital screening in extended family members, followed by prenatal diagnosis is acceptable and the most effective strategy for control of thalassemia in developing countries like India

Details of <i>HEXA</i> missense mutations detected in infantile TSD patients and <i>in silico</i> analysis.

<p>DC  =  Disease causing, P  =  Polymorphism, IT  =  Intolerant, T  =  Tolerant, PD  =  Probably damaging RMSD  =  root mean square deviation.</p><p>The MutationT@sterscore is taken from an amino acid substitution matrix (Grantham Matrix <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039122#pone.0039122-Myerowitz1" target="_blank">[3]</a>) which takes into account the physico-chemical characteristics of amino acids and scores substitutions according to the degree of difference between the original and the new amino acid. Scores may range from 0.0 to 6.0.</p><p>The SIFT score is the normalized probability that the amino acid change is tolerated and ranges from 0 to 1. The amino acid substitution is predicted damaging is the score is < = 0.05, and tolerated if the score is >0.05.</p><p>The Polyphen2 score is the Naïve Bayes posterior probability that this mutation is damaging and thus ranges from 0 to 1.</p

Stereoscopic view of the docking experiments.

<p>Green sticks indicate C^α trace of amino acids involved in the active site and CPK (Corey-Pauling-Koltun) coloring scheme represents ligand GalNAc (N acetyl galactosamine) portion of GM2 ganglioside. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039122#pone-0039122-g004" target="_blank">Fig 4a:</a> Wild type (αHex-A-GalNAc complex). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039122#pone-0039122-g004" target="_blank">Fig 4b:</a> Mutant (αD322N-GalNAc), Red shows mutation p.D322N, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039122#pone-0039122-g004" target="_blank">Fig 4c:</a> Mutant (αD322Y-GalNAc), Cyan shows mutation p.D322Y, Fig. 4d: Mutant (α E462V-GalNAc), yellow shows mutation p.E462Y.</p

Multiple protein sequence alignment using ClustalW shows evolutionary conservation of amino acid residues.

<p>Fig. 3a: αE114 and αR170; Fig. 3b: αD322 and αR393; Fig. 3c: αE462 and αG478.</p