Journal of pediatric genetics最新文献

Beta-thalassemic patients require regular blood transfusion to sustain their life which leads to iron overload and causes oxidative stress. The aim of this study was to investigate the status of variants in genes including GSTM1 , GSTT1 (null/present), CT-262 (C > T) and CT-89 (A > T), glutathione peroxidase (GPx), and myeloperoxidase (MPO). The genotype studies were conducted with 200 thalassemia major (TM) patients and 200 healthy controls. Genotyping of GST gene was performed by multiplex polymerase chain reaction (PCR), whereas for CT, GPx and MPO genesvariants PCR- restriction fragment length polymorphism technique used. However, the enzyme activities were measured only in the patients group to assess the association with the genotypes. All enzyme estimations were performed by ELISA. We observed higher frequency of GSTT1 null, CT-89 (A > T), GPx1 198 (C > T) and MPO-463 (G > A) polymorphisms in TM patient than healthy controls. However, CT-262 (C > T) polymorphism was not found to be statistically significantly different between patients and controls. Our results suggest that frequency of null allele of glutathione-S-transferase is significantly high among TM patients. The other alleles CT-89 (A > T), GPx1 198 (C > T), and MPO-463 (G > A) are linked to decreased CT, GPX, and MPO enzyme activities.

This cross-sectional study aimed to observe number of marriages between relatives in São Francisco Valley municipalities and correlations between degrees of kinship and susceptibility to genetic diseases. Three hundred and nine (309) consanguineous couples were interviewed in five municipalities. The data were analyzed using SPSS (version 22), Chi-square testing, and the generalized estimating equation (GEE). In Pariconha-AL for first cousins, the results revealed significantly higher numbers of disabled children than for third cousins ( p  < 0.05). Of these, the prevalence for physical disability was significant ( χ 2 = 19.203, d f  = 4, p  = 0.001). In the cities of Glória-BA ( χ 2 = 11.652, d f  = 3, p  = 0.020) and OlhoD'água do Casado-AL ( χ 2 = 8.123, d f  = 4, p  = 0.044), physical disabilities were also significantly higher in children from unions of first-degree cousins than for other degrees of kinship. Visual impairment was more significant in first-degree cousins in Glória-BA ( χ 2 = 14.206, d f  = 3 p  = 0.007); yet among third-degree cousins, visual impairment in the municipality of Santa Brígida-BA was more prevalent ( χ 2 = 6.416, d f  = 2 p  = 0.040). Inbreeding, as revealed in the evaluated cities, reinforces the hypothesis for developing genetic diseases.

Cribriform appearance of the brain in Canavan disease is a rare finding. The two presented cases broaden the magnetic resonance imaging (MRI) phenotype wherein numerous oval, cystic structures, a few resembling dilated Virchow-Robin (VR) spaces, were noted in the centrum semiovale, periventricular, and lobar white matter producing a cribriform pattern. Besides, discrete round to oval cysts were present at the gray-white matter junctions in the second case, which were larger and appeared morphologically distinct from the VR spaces. These cysts did not elongate in any plane on imaging and were more representative of giant intramyelinic vacuoles. Genetic analysis revealed novel mutations in the aspartoacylase or ASPA gene that possibly accounts for the severe form of Canavan disease, which probably explains the imaging findings. The multicystic appearance of the white matter in Canavan disease is unusual and possibly represents two different histopathological substrates.

Primary distal renal tubular acidosis (dRTA) or Type 1 RTA in children is caused by a genetic defect (involved genes ATP6V0A4 , ATP6V1B1 , SLC4A1 , FOXI1 , or WDR72 ), which causes tubular transport defects characterized by an inability to appropriately acidify urine with resultant persistent hyperchloremic metabolic acidosis. Retrospective analysis of 28 children (14 males) under the age of 14 years with dRTA seen from 2010 to 2019 was reviewed, and detailed clinic records were analyzed. The clinical features, investigations, and response to treatment were recorded. The median age of the children at presentation was 30 months (range: 9.25-72 months), and the median age at onset of symptoms was 2 months. All the children had growth failure, polyuria, and polydipsia at presentation. Mean serum potassium, pH, bicarbonate, and anion gap at presentation was 2.3 ± 0.5 mmol/L, 7.22 ± 0.09, 13.28 ± 4.37 mmol/L, and 9.3 ± 2.18, respectively. Mean serum potassium, pH, bicarbonate at follow-up was 3.88 ± 0.6 mmol/L, 7.35 ± 0.06, and 20.13 ± 4.17 mmol/L, respectively. The median z-score for the weight for age and height for age at initial presentation was -4.77 (-7.68 to -3.74) and -4.21 (-5.42 to -2.37) and at follow-up was -3.35 (-5.29 to -1.55) and -3.84 (-5.36 to -1.63), respectively. Twenty-two (78.6%) children had medullary nephrocalcinosis. Four children had sensorineural hearing loss. Seven children had genetic testing done, and six had pathogenic or likely pathogenic variants in ATP6V1B1 and ATP6V0A4 gene. Children with dRTA have a guarded prognosis and ATP6V1B1 and ATP6V0A4 mutations are the most common implicated genetic defect in Indian children with distal RTA.

Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common ciliopathies with kidney (nephromegaly, hypertension, renal dysfunction) and liver involvement (congenital hepatic fibrosis, dilated bile ducts). Clinical features also include growth failure and neurocognitive impairment. Plurality of clinical aspects requires multidisciplinary approach to treatment and care of patients. Until recently, diagnosis was based on clinical criteria. Results of genetic testing show the molecular basis of polycystic kidneys disease is heterogeneous, and differential diagnosis is essential. The aim of the article is to discuss the role of genetic testing and its difficulties in diagnostics of ARPKD in children.

Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X-type motif 15 ( NUDT15 ) genes have been proposed as key determinants of 6-mercaptopurine (6-MP)-induced myelosuppression in pediatric acute lymphoblastic leukemia (ALL). In the present study, genotypes of TPMT and NUDT15 were investigated in 178 Thai pediatric patients with ALL by the TaqMan SNP genotyping assay and DNA sequencing. The frequency of TPMT*3C was 0.034. Among NUDT15 variants, NUDT15*3 is the most common variant with the allele frequency of 0.073, whereas those of NUDT15*2 , NUDT15*5 , and NUDT15*6 variants were 0.022, 0.011, and 0.039. These data suggest that a high proportion of Thai pediatric ALL patients may be at risk of thiopurine-induced myelosuppression.

Ectopic calcification in soft tissue is associated with several disorders including pseudohypoparathyroidism (PHP), which is characterized by resistance or nonresponse to parathyroid hormone (PTH) function. Association between PHP and 22q11DS, also known as DiGeorge syndrome, is rare, especially in children. We describe a newborn girl diagnosed with 22q11DS, presenting ectopic calcifications in soft tissue and suspicion of PHP. PTH function showed values close to the upper limit of the reference value. Radiology showed bone callus in the right wrist. PHP can be a new clinical finding associated with 22q11DS. Parathyroid function investigation in individuals with 22q11DS, presenting bone dysmorphisms and/or calcium metabolism alterations, should be considered.

Multiplex ligation-dependent probe amplification (MLPA) detects exonic deletions and duplications in the DMD gene in around 65 to 70% of patients with the Duchenne muscular dystrophy (DMD) phenotype. This study looks at the diagnostic yield of next-generation sequencing (NGS) and the mutation spectrum in an Asian Indian cohort of MLPA-negative cases with the DMD phenotype. NGS-based sequencing of DMD gene was done in 28 MLPA-negative cases (25 male probands with the DMD phenotype and 3 obligate carrier mothers of deceased affected male patients) and disease-causing variants were identified in 19 (67.9%) of these cases. Further molecular testing in four of the remaining nine cases revealed gene variants associated with limb girdle muscular dystrophies. Thus, NGS-based multigene panel testing for muscular dystrophy-associated genes or clinical exome sequencing rather than targeted DMD gene sequencing appears to be a more cost-effective testing modality with better diagnostic yield, for MLPA-negative patients with the DMD phenotype.

The deletion of the long arm of chromosome 4 is rare, presenting with a variable phenotype depending on the chromosomic area affected. A term newborn with prenatal diagnosis of anhydramnios, dysplastic cystic kidneys, and cardiomegaly was born with generalized subcutaneous edema, several dysmorphic features, and progressive renal failure requiring dialysis. The infant continued to deteriorate and died at 52 days of age. Autopsy confirmed bilateral renal dysplasia with cysts. Array-comparative genomic hybridization (CGH) identified a large deletion on 4q25-q28.3, which is not yet described in association with renal disease. The clinical progression could be expected due to the severity of the perinatal clinical presentation.

Complete labyrinthine aplasia (CLA) is a rare inner ear anomaly. The only identified genetic cause of CLA with severe sensorineural hearing loss is labyrinthine aplasia, microtia, and microdontia (LAMM) syndrome. Here we reported a child who presented with syndromic hearing loss and was diagnosed with LAMM syndrome. Genetic evaluation provided the family with confirmation of the diagnosis, provision of the prognosis, genetic counselling, and prenatal diagnosis. This report highlighted that CLA should be recognized as a unique sign to diagnose LAMM syndrome, to analyze FGF3 gene mutation, and also demonstrated the utility of genetic testing in patients with suspected LAMM syndrome to provide exact diagnosis and further management.