Singleton exome sequencing of 90 fetuses with ultrasound anomalies revealing novel disease-causing variants and genotype–phenotype correlations

Exome sequencing has been increasingly implemented in prenatal genetic testing for fetuses with morphological abnormalities but normal rapid aneuploidy detection and microarray analysis. We present a retrospective study of 90 fetuses with different abnormal ultrasound findings, in which we employed the singleton exome sequencing (sES; 75 fetuses) or to a lesser extent (15 fetuses) a multigene panel analysis of 6713 genes as a primary tool for the detection of monogenic diseases. The detection rate of pathogenic or likely pathogenic variants in this study was 34.4%. The highest diagnostic rate of 56% was in fetuses with multiple anomalies, followed by cases with skeletal or renal abnormalities (diagnostic rate of 50%, respectively). We report 20 novel disease-causing variants in different known disease-associated genes and new genotype–phenotype associations for the genes KMT2D, MN1, CDK10, and EXOC3L2. Based on our data, we postulate that sES of fetal index cases with a concurrent sampling of parental probes for targeted testing of the origin of detected fetal variants could be a suitable tool to obtain reliable and rapid prenatal results, particularly in situations where a trio analysis is not possible.

A Novel GEMIN4 Variant in a Consanguineous Family Leads to Neurodevelopmental Impairment with Severe Microcephaly, Spastic Quadriplegia, Epilepsy, and Cataracts

Pathogenic variants in GEMIN4 contribute to a hereditary disorder characterized by neurodevelopmental features, microcephaly, cataracts, and renal abnormalities (known as NEDMCR). To date, only two homoallelic variations have been linked to the disease. Moreover, clinical features associated with the variants have not been fully elucidated yet. Here, we identified a novel variant in GEMIN4 (NM_015721:exon2:c.440A>G:p.His147Arg) in two siblings from a consanguineous Saudi family by using whole exome sequencing followed by Sanger sequence verification. We comprehensively investigated the patients’ clinical features, including brain imaging and electroencephalogram findings, and compared their phenotypic characteristics with those of previously reported cases. In silico prediction and structural modeling support that the p.His147Arg variant is pathogenic.

Maturity-Onset Diabetes of Young Type 5: Diabetes with Extrapancreatic Features

Objective. This case involves a new-onset diabetes patient diagnosed during pregnancy with the congenital dysplastic right kidney. Case Report. Clinical presentation, biochemical features, imaging in a patient with diabetes diagnosed during pregnancy, and congenital dysplastic right kidney. Discussion. We present a case of a 22-year-old female with the congenital dysplastic right kidney diagnosed with gestational diabetes mellitus after failing a 1-hour oral glucose tolerance test, requiring insulin during pregnancy. Because of the family history of diabetes and morphologic renal abnormalities at young ages on the maternal side of the family, our patient was evaluated for maturity-onset diabetes of adult and was found to have HNF-1β mutation. Conclusion. This case highlights the importance of considering the diagnosis of maturity-onset diabetes of young and particularly MODY-5 in individuals with extrapancreatic features. MODY-5 should also be considered in a patient undergoing renal transplant at young ages with a family history of morphologic renal abnormalities.

Renal abnormalities associated with Mayer-Rokitansky-Küster-Hauser syndrome

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare congenital disorder affecting female reproductive system (agenesis of uterus and upper part of vagina) alone (type 1), or associated with abnormalities of other organs and systems (type 2). We report a case of a 21-year-old woman diagnosed with MRKH due to primary amenorrhea during puberty and operated for formation of neovagina. She was admitted to the Department of Urology with abdominal pain and oligoanuria, where the physical examination and imaging studies revealed a malformation of the upper urinary tract: a solitary dystopia of kidney in the pelvis with stenosis of ureteropelvic junction and hydronephrosis. After initial desobstruction with a DJ stent, a pyeloplasty was performed. Females with primary amenorrhea are often delayed with the diagnosis of potential MRKH syndrome, and those diagnosed with the syndrome should undergo detailed examination to exclude concomitant urinary abnormalities.

EFFECT OF KIDNEY DISEASE ON THE MORTALITY OF COVID POSITIVE PATIENTS IN A TERTIARY CARE HOSPITAL, INDIA

INTRODUCTION: CKD and kidney failure are signicant comorbidities associated with unfavourable outcomes in patients with COVID-19. Patients with CKD/kidney failure also have a disproportionate burden of other comorbidities 1 (e.g., coronary artery disease, hypertension, and diabetes mellitus) associated with more severe presentations of COVID-19 . SARS-CoV-2 infection frequently triggers a massive release of proinammatory cytokines and may induce coagulation abnormalities that increase the risk of 2 cardiovascular events and multiorgan dysfunction. MATERIALS & METHODS: It is a retrospective study done in government general hospital Vijayawada from patients admitted with covid positive status having comorbidities, with the help of medical records department, done during 1st April 2020 to 31st March 2021. RESULTS : Out of 150 patients who had a renal abnormality, 40 (27%)had AKI, 110 ( 73%) had CKD, and of these patients, 96( 64%) patients underwent dialysis, 54( 36%) patients did not undergo dialysis, having high mortality mainly in patients having CKD than AKI. Compared to patients with comorbidity without renal abnormality and patients with renal abnormalities, the mortality was high in the later group of patients. CONCLUSION: There is a signicant effect of kidney disease on mortality in covid positive patients. Patients having CKD will have higher mortality compared with AKI. Even though the mortality was seen in patients having comorbidities without renal involvement, mortality was much higher in patients with renal involvement.

Fetal ciliopathies: a retrospective observational single-center study

Purpose Report on the diagnosis of prenatally suspected multisystem ciliopathies in a single center between 2002 and 2020. Methods Retrospective observational single-center study including pregnancies with prenatal ultrasound features of multisystem ciliopathies, such as hyperechogenic kidneys together with polydactyly and/or other skeletal and extraskeletal findings. Cases were compared according to their prenatal findings and outcomes. Results 36 cases of multisystem ciliopathies were diagnosed. Meckel-Gruber syndrome (MKS) was the most common ciliopathy (n = 19/36, 52.8%), followed by disorders that belong to the group of short-rib thoracic dysplasia (SRTD, n = 10/36, 27.8%) McKusick–Kaufmann syndrome (MKKS, n = 4/36, 11.1%), Bardet–Biedl syndrome (BBS, n = 2/36, 5.5%) and Joubert syndrome (n = 1/36, 2.8%). All cases showed abnormalities of the kidneys, most often hyperechogenic parenchyma (n = 26/36, 72.2%), cystic dysplasia (n = 24/36, 66.7%), and/or bilateral kidney enlargement (n = 22/36, 61.1%). Oligohydramnios was mainly present in fetuses with MKS. Polydactyly (n = 18/36), abnormalities of the CNS (n = 25/36), and heart defects (n = 10/36) were associated in 50%, 69.4%, and 27.8%, respectively. Conclusion Prenatal detection of renal abnormalities associated with skeletal or brain abnormalities should raise the suspicion for multisystem ciliopathies. Prenatal ultrasound can help to differentiate between different diseases and pave the way for subsequent targeted genetic testing.