A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1

Abstract Background Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare hereditary disorder characterized by defects in teeth, hair, and nails in association with a fusion of the digits. Genetically, the disease phenotypes are caused by homozygous and compound heterozygous variants in NECTIN4 gene. Objective The main objective of the study was to identify the pathogenic sequence variant(s) for family screening and identification of carriers. Methods In the present study, the authors have investigated a large consanguineous family of Pakistani origin segregating autosomal recessive EDSS1. All the coding exons of the NECTIN4 gene were directly sequenced using gene-specific primers. Results The affected individuals presented the classical EDSS1 clinical features including sparse hair, hypoplastic nails with thick flat discolored nail plates, peg-shaped, conical, and widely spaced teeth with enamel hypoplasia, proximal cutaneous syndactyly of fingers and toes. Sequence analysis of the coding region of the NECTIN4 identified a novel nonsense variant [c.163C>T; p.(Arg55*)] in exon-2 of the gene. Computational analysis of protein structure revealed that the variant induced premature termination at Arg55 located in Ig-like V-loop region leading to loss of Ig-C2 type domains and transmembrane region, and most likely Nectin-4 function will be lost. Study limitation Gene expression studies are absent that would have strengthened the findings of computational analysis. Conclusion The present study expanded the phenotypic and mutation spectrum of the NECTIN4 gene. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families.

Laparoscopic Surgery in Pediatric Age Group – Our 10 Years Experience from a Tertiary Care Centre

Background: To study the role of Laparoscopic surgery in Pediatric age group. Settings: Department of General and Minimal Access Surgery, Government Medical College Srinagar. Methods: Three hundred and sixty four pediatric patients referred to our tertiary care center in the pediatric age group were operated upon laparoscopically for various conditions from January 2009 to January 2019. Results: A total of 364 non-infantile pediatric cases were operated upon laparoscopically which included 107 Non-palpable UDT, 71 Appendectomies, 67 Diagnostic laparoscopies, 31 Cholecystectomies, 5 VATS procedures, 8 Varicocelectomies, 2 Advance urological procedures, 55 Herniotomies, 3 umbilical hernia laparoscopic anatomical repairs, 7 Hepatic Hydatid cyst surgeries, 5 Laparoscopic assisted Soaves procedures, 1 each of Laparoscopic Pyeloplasty, Morgagni hernia repair and Ladd’s procedure for Malrotation of Gut. There were 5 conversions to open procedure and 8 cases were completed by laparoscopic assisted methods. The complication rate including minor complications was approximately 4%. Conclusion: Laparoscopy including Videoassisted Thoracoscopic Surgeries (VATS) in pediatric age group is safe, feasible and rapidly gaining popularity even for advanced and reconstructive procedures. However the threshold for better judgement should be low for decreasing avoidable morbidity in small children.

Aerobic Bacterial Profile Of Aspirated Pus Samples At A Tertiary Care Hospital, Patna, Bihar

Abscess is an accumulation of pus in tissue and it is caused by suppuration deep within a tissue, an organ or confined space. Though the bacterial profile from pus samples remains almost similar in various studies, the irrational use of antibiotics has lead to the emergence of various drug resistant pathogens. In this retrospective study we have taken 290 aspirated pus samples for aerobic culture and sensitivity and found 23 different aerobic bacterial isolates. Most common isolate was Escherichia coli (n-12) followed by Staphylococcus aureus (n-8) and one each was Acinetobacter spp., Klebsiella pneumoniae and Streptococcus spp. Sensitivity of E coli was found to be low for ciprofloxacin, amoxycillin+clavulanic acid, ceftazidime, cefepime and aztreonam; while sensitivity was high for amikacin, imipenem, colistin and tigecycline. Staphylococcus aureus was highly sensitive to most of the antibiotics that had been put for sensitivity testing. A continuous inspection should be carried out to monitor the antimicrobial susceptibility of bacterial isolates from aspirated pus samples to choose appropriate antibiotics for prophylaxis and treatment of infections.

Homozygous sequence variants in the WNT10B gene underlie split hand/foot malformation

Abstract Split-hand/split-foot malformation (SHFM), also known as ectrodactyly is a rare genetic disorder. It is a clinically and genetically heterogeneous group of limb malformations characterized by absence/hypoplasia and/or median cleft of hands and/or feet. To date, seven genes underlying SHFM have been identified. This study described four consanguineous families (A-D) segregating SHFM in an autosomal recessive manner. Linkage in the families was established to chromosome 12p11.1-q13.13 harboring WNT10B gene. Sequence analysis identified a novel homozygous nonsense variant (p.Gln154*) in exon 4 of the WNT10B gene in two families (A and B). In the other two families (C and D), a previously reported variant (c.300_306dupAGGGCGG; p.Leu103Argfs*53) was detected. This study further expands the spectrum of the sequence variants reported in the WNT10B gene, which result in the split hand/foot malformation.

Psychological impact of sub fertility on the couples

Objective: To evaluate the psychological aspect of subfertility and treatment on the couples. Methodology: This Prospective survey study was carried out in the department of Obstetrics and Gynaecology at a private hospital in Lahore, Pakistan. 40 couples undergoing fertility treatment were enrolled. A Self-report questionnaire included age, level of education, social status, duration of marriage , duration of infertility, causes of infertility, duration of treatment, social stress, effect of infertility on marital relationship, expected likelihood of achieving pregnancy, anticipation of stress during treatment, and emotional reactions to infertility was given to all the participants of the study

Results: The majority [70%] of women undergoing fertility treatment were of ages 25-34 years. 62.5% couples were married for 1 to 5 years. Majority of couples were educated and belonged to the middle-class family. 55% had been undergoing treatment for 3 years and more. In half, the causes of infertility were known. 67.5% had failed treatment and 32.5% became pregnant with treatment. All the couples experienced emotional trauma with treatment and needed psychological help despite the outcome. 62.5% suffered with depression, 30% anxiety and 7.5% had anger. 15% women needed psychiatric medication besides counselling and behavioural therapy. 60% couples had sexual dysfunction leading to marital problems. 80% couples complained of behaviour changes. Specific questionnaires were structured for assessing different psychological aspects on infertile women, men or couples. The hospital Anxiety and Depression Scale and demographic and fertility information questionnaire was given to all infertile couples. The psychological impact was more on females 82.5% compared to males 17.5%. All the couples underwent social pressure

Conclusions: Psychological factors play an important role in the infertility. It is important to manage this devastating problem, which has cultural and social impact

Induction of labour with prostaglandin E2 vaginal tablet in women with previous one caesarean section

Objective: to evaluate the frequency of vaginal birth after induction of labour with vaginal tablet prostaglandin E2 in women with previous one caesarean section

Methods: total 100 pregnant women were selected for the study with singleton, cephalic pregnancy and history of previous one caesarean section at gestational age between 37 to 41 weeks. EFW was less than 3.7kg and Bishop Score was> 5. Cervical ripening was done with PGE2 vaginal tablet Prostin E2 [3mg] after initial CTG. These women were evaluated after 6 hours by Bishop Score. CTG was repeated, if reactive, 2nd dose of PGE2 vaginal tablet was given. If patients went into labour after first or 2nd dose of prostin E2, labour was carefully monitored by close one to one monitoring by vital signs, uterine contractions, FHR monitoring, scar tenderness and Bishop Score. Outcomes measured were frequency of VBAC [vaginal birth after caesarean section], uterine rupture, neonatal outcome and frequency of emergency repeat caesarean section

Results: mean age of pregnant women was 28.06 + 3.45 years. 64 patients delivered vaginally and 36 delivered by emergency repeat caesarean section. Fetal distress was the main reason for emergency repeat caesarean section [ERCS]. There was one case of uterine rupture. Neonatal outcome were measured by Apgar score, admission to nursery and survival rate. One baby died in utero because of uterine rupture and another baby died in nursery on 2nd day of life due to meconium aspiration syndrome. 98 babies were delivered with good Apgar score and survival rate of 98% was found

Conclusion: our study concluded that prostaglandin E2 vaginal tablets are safe for inducing labour in women with previous one caesarean section but it should be administered with caution. Risk of uterine rupture is 1 % in our study