Novel HOXD13 variants in syndactyly type 1b and type 1c, and a new spectrum of TP63-related disorders.

Syndactyly is the most common limb defect depicting the bony and/or cutaneous fusion of digits. Syndactyly can be of various types depending on the digits involved in the fusion. To date, eight syndactyly-associated genes have been reported, of which HOXD13 and GJA1 have been explored in a few syndactyly but most of them have unknown underlying genetics.

Fundus Examination to Guide Anticoagulation Therapy in Suspected COVID-19 in a Critical Care Unit.

Saha R, Singh SK, Samanta S. Fundus Examination to Guide Anticoagulation Therapy in Suspected COVID-19 in a Critical Care Unit. Indian J Crit Care Med 2021;25(6):737-738.

Novel GLI3 pathogenic variants in complex pre- and postaxial polysyndactyly and Greig cephalopolysyndactyly syndrome.

Polydactyly is a limb malformation and can occur as nonsyndromic polydactyly, syndromic polydactyly, or along with other limb defects. A few genes have been identified that cause various forms of syndromic and nonsyndromic polydactyly, of which GLI3 has been extensively explored. In the present study, GLI3 gene was screened by direct resequencing in 15 polydactyly cases with or without other anomalies.

TGFβ3, MSX1, and MMP3 as Candidates for NSCL±P in an Indian Population.

Objective: To evaluate the association of transforming growth factor β3 ( TGFβ3), muscle segment homeobox 1 ( MSX1), Metalloproteinases 3 ( MMP3), and MMP9 genes as candidates for nonsyndromic cleft lip and/or palate in an Indian population.

Design: Case-control association study, mutational screening, and functional evaluation of obtained mutations.

Setting: Mutational screening of the developmental genes, TGFβ3 and MSX1, along with functional evaluation and association of promoter region SNPs-one each in MMP3 and MMP9.

Genetic heterogeneity in Van der Woude syndrome: identification of NOL4 and IRF6 haplotype from the noncoding region as candidates in two families.

Van der Woude syndrome (VWS) shows an autosomal dominant pattern of inheritance with two known candidate genes, IRF6 and GRHL3. In this study, by employing genome-wide linkage analyses on two VWS affected families, we report the cosegregation of an intronic rare variant in NOL4 in one family, and a haplotype consisting of three variants in the noncoding region of IRF6 (introns 1, 8 and 3'UTR) in the other family. Using mouse, as well as human embryos as a model, we demonstrate the expression of NOL4 in the lip and palate primordia during their development.

A novel non-coding RNA within an intron of CDH2 and association of its SNP with non-syndromic cleft lip and palate.

Background: Genome-wide linkage analysis and whole genome sequencing in a Van der Woude syndrome (VWS) family revealed that the SNP, rs539075, within intron 2 of the cadherin 2 gene (CDH2) co-segregated with the disease phenotype.

Results: A study with nonsyndromic cleft lip with or without cleft palate (NSCL ± P) cases (N = 292) and controls (N = 287) established association of this SNP with NSCL ± P as a risk factor. RT-PCR based expression analysis of the SNP-harbouring region of intron 2 of CDH2 in the clefted lip and/or palate tissues of 16 patients revealed that the mutant allele expressed in all those individuals having it (hetero-/homozygous), whereas the wild type allele expressed in <50% of the samples in which it was present.

Comparative Study of GeneXpert MTB/RIF Assay and Multiplex PCR Assay for Direct Detection of Mycobacterium tuberculosis in Suspected Pulmonary Tuberculosis Patients.

Pulmonary tuberculosis (PTB) is one of the major infectious diseases in developing countries. The objective of this study was to compare rapid diagnostics technique, GeneXpert MTB/RIF (GeneXpert) and Multiplex PCR assay (MPCR) targeting IS6110 segment and mpb64 gene for direct detection of Mycobacterium tuberculosis (MTB) in suspected PTB patients. A cross sectional study was carried among 105 sputum samples from suspected PTB patients to evaluate GeneXpert and Multiplex PCR who visited National Tuberculosis Center, Nepal.

GLI3 mutations in syndromic and non-syndromic polydactyly in two Indian families.

The GLI3 protein is a zinc finger transcription factor, expressed early in development. The GLI3 gene exhibits allelic heterogeneity as mutations in this gene are associated with several developmental syndromic and non-syndromic polydactyly. The present study reports two cases: first, a familial case of Greig Cephalopolysyndactyly Syndrome (GCPS); the second is a sporadic case with both postaxial polydactyly (PAP) type A and B.

Recent advances in management of diabetic macular edema.

Diabetic macular edema (DME) is the leading cause of moderate vision loss in diabetics. Modalities to image and monitor DME have evolved much in the last decade. Systemic control is the most important part of management.

Serial ultra wide field imaging for following up acute retinal necrosis cases.

We describe two cases of acute retinal necrosis (ARN) in a post renal transplant diabetic patient and a pregnant female in the first trimester. Serial ultra wide field imaging (UWFI) with comprehensive ocular examination was done to monitor the progression of the disease. All the cases responded favorably with intravenous followed by oral acyclovir, which was captured with UWFI.

A novel GLI3c.750delC truncation mutation in a multiplex Greig cephalopolysyndactyly syndrome family with an unusual phenotypic combination in a patient.

Greig cephalopolysyndactyly (GCPS) syndrome is an autosomal dominant disorder with high penetrance in majority of cases, characterized by a triad of polysyndactyly, macrocephaly and hypertelorism. GCPS is known to be caused by mutations in the transcription factor GLI3 gene (7p13) which results in functional haploinsufficiency of this gene. The present study reports a large multiplex family having 12 members affected with GCPS in 3 generations and several unaffected members showing autosomal dominant pattern of inheritance with complete penetrance.

Lower incidence of nonsyndromic cleft lip with or without cleft palate in females: is homocysteine a factor?

In India, as in other parts of the world, nonsyndromic cleft lip with or without cleft palate (NSCL +/- P) is a highly prevalent birth defect, its incidence in males being twice that in females. A case-control association study has been carried out with respect to homocysteine level and MTHFR C677T, A1298C and SLC19A1 (RFC1) G80A genotypes from an eastern Indian cohort to investigate whether Hcy and other Hcy-pathway genes also contribute to the risk level. While MTHFR 677T and SLC19A1 80G are individually and cumulatively risk factors, SLC19A1 80A appears to be protective against MTHFR 677T risk allele.

Coding region of IRF6 gene may not be causal for Van der Woude syndrome in cases from India.

Objective: Evaluation of the IRF6 gene in Van der Woude syndrome cases from an Indian population.

Subjects: Nine affected and four unaffected individuals from seven families with Van der Woude syndrome as well as five normal controls (with no history of Van der Woude or any other congenital malformation and belonging to the same geographical area as the families with Van der Woude syndrome).

Method: Direct sequencing of all coding regions and exon-intron boundaries of the IRF6 gene.

Smile Train: The ascendancy of cleft care in India.

Though India has an estimated population of one million untreated cleft patients, facilities for its treatment have been limited and are not evenly distributed across the country. Furthermore, a paucity of committed cleft surgeons in fewer hospitals to provide quality surgical treatment to these patients, poverty, illiteracy, superstitions and poor connectivity in some remote regions severely limit the chances of an average cleft lip patient born in India from receiving rational and effective comprehensive treatment for his/her malady. The Smile Train Project with its singular focus on cleft patients started its philanthropic activities in India in the year 2000.

MTHFR 677TT alone and IRF6 820GG together with MTHFR 677CT, but not MTHFR A1298C, are risks for nonsyndromic cleft lip with or without cleft palate in an Indian population.

Aim: To determine the association of three SNPs, IRF6 G820A, MTHFR C677T, and MTHFR A1298C, with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in an Indian population.

Method: A total of 323 NSCL/P patients, 116 of their mothers, 108 of their fathers, and 214 normal controls have been examined for the above three SNPs.

Result: Frequency of IRF6 GG was 65% in controls, 78% in cases, 84% in case-fathers, and 80% in case-mothers.