• Childhood Kidney Diseases
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• v.26 no.1
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• pp.40-45
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• 2022

Purpose: Chronic kidney disease (CKD) has various underlying causes in children. Identification of the underlying causes of CKD is important. Genetic causes comprise a significant proportion of pediatric CKD cases. Methods: In this study, we performed whole-exome sequencing (WES) to identify genetic causes of pediatric CKD. From January to June 2021, WES was performed using samples from pediatric patients with CKD of unclear etiology. Results: Genetic causes were investigated using WES in 37 patients (17 males) with pediatric CKD stages 1 (n=5), 2 (n=7), 3 (n=2), 4 (n=2), and 5 (n=21). The underlying diseases were focal segmental glomerulosclerosis (n=9), congenital anomalies of the kidney and urinary tract including reflux nephropathy (n=8), other glomerulopathies (n=7), unknown etiology (n=6), and others (n=7). WES identified genetic causes of CKD in 12 of the 37 patients (32.4%). Genetic defects were discovered in the COL4A4 (n=2), WT1 (n=2), ACTN4, CEP290, COL4A3, CUBN, GATA3, LAMA5, NUP107, and PAX2 genes. WT1 defects were found in patients whose pathologic diagnosis was membranoproliferative glomerulonephritis, and identification of CUBN defects led to discontinuation of immunosuppressive agents. Genetic diagnosis confirmed the clinical diagnosis of hypoparathyroidism, sensorineural deafness, and renal disease; Alport syndrome; and Joubert syndrome in three of the patients with CKD of unknown etiology (COL4A4 [n=2], CUBN [n=1]). Extrarenal symptoms were considered phenotypic presentations of WT1, PAX2, and CEP290 defects. Conclusions: WES provided a genetic diagnosis that confirmed the clinical diagnosis in a significant proportion (32.4%) of patients with pediatric CKD.

• Molecules and Cells
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• v.38 no.9
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• pp.781-788
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• 2015

Mutations of MYO15A are generally known to cause severe to profound hearing loss throughout all frequencies. Here, we found two novel MYO15A mutations, c.3871C>T (p.L1291F) and c.5835T>G (p.Y1945X) in an affected individual carrying congenital profound sensorineural hearing loss (SNHL) through targeted resequencing of 134 known deafness genes. The variant, p.L1291F and p.Y1945X, resided in the myosin motor and IQ2 domains, respectively. The p.L1291F variant was predicted to affect the structure of the actin-binding site from three-dimensional protein modeling, thereby interfering with the correct interaction between actin and myosin. From the literature analysis, mutations in the N-terminal domain were more frequently associated with residual hearing at low frequencies than mutations in the other regions of this gene. Therefore we suggest a hypothetical genotype-phenotype correlation whereby MYO15A mutations that affect domains other than the N-terminal domain, lead to profound SNHL throughout all frequencies and mutations that affect the N-terminal domain, result in residual hearing at low frequencies. This genotype-phenotype correlation suggests that preservation of residual hearing during auditory rehabilitation like cochlear implantation should be intended for those who carry mutations in the N-terminal domain and that individuals with mutations elsewhere in MYO15A require early cochlear implantation to timely initiate speech development.

• Journal of Life Science
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• v.31 no.5
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• pp.453-463
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• 2021

Hearing loss is a group of clinically and genetically heterogeneous disorders characterized by congenital- to adult-onset deafness with frequent additional symptoms such as myopathy, nephropathy, and optic disorders. It is commonly divided into two types: syndromic, with no other symptoms, and nonsyndromic, with other symptoms. Autosomal recessive hearing loss is relatively frequent in Pakistan, which may be due in part to frequent consanguineous marriages. This study was performed by whole exome sequencing to determine the genetic causes in two Pakistani consanguineous families with autosomal recessive hearing loss. We identified a pathogenic homozygous variant (p.Leu326Gln in MYO7A) in a family with prelingual-onset hearing loss and two variants of uncertain significance (p.Val3094Ile in GPR98 and p.Asp56Gly in PLA2G6) in a family with early-onset hearing loss concurrent with muscular atrophy. The missense mutations in MYO7A and PLA2G6 were located in the highly conserved sites, and in silico analyses predicted pathogenicity, while the GPR98 mutation was located in the less conserved site, and most in silico analysis programs predicted its nonpathogenic effect. Homozygosity mapping showed that both alleles of the homozygous mutations identified in each family originated from a single founder; spread from this single source might be due to consanguineous marriages. This study will help provide exact molecular diagnosis and treatment for autosomal recessive hearing loss patients in Pakistan.

• Journal of Preventive Medicine and Public Health
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• v.6 no.1
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• pp.51-63
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• 1973

This paper illustrate residual hearing and socio-medical background on the hearing impaired children, 207 comming to Deaf School. attached to Hankuk Social Work College, Taegu, Korea. The survey was performed through interview with their parents and testing by diagnostic audio-meter (TRIO, AS 105 type) at soundproof room from March 10, to November 28, 1973. The results obtained were as follows. 1) The attendance rate of the compulsory primary school was markedly lower tendency in female than male according to directly proportional to prevalence rate of deafness among them. If was showed the deeper gap in the more superior school (middle and high school). 2) Who entered at the suitable age to each school (six years old to primary school, 12 years to middle and 15 years to high) was 11.3%. And who were enrolled in school age to each school (6-11 years for primary. 12-14 years for middle and 15-17 years for high) was 45.9% (43.7% in male, 50.0% in female). 3) As causative disease, congenital case, were 23.6% included of 13.5% of heredity and 10.1% of troubles during pregnancy; the total acquired cases were 47.9%, it was classified as 11.6% of convulsion from any other diseases, 7.7% of measles, 7.7% of other febrile diseases, 3.4% of drug (the most of streptomycin) intoxication, 2.4% of meningitis, 1.5% of epidemic encephalitis and 31.3% of other diseases; and unknown cases were 28.5%. 4) 31.4% of who included congenital cases lost their hearing within six months old, 11.6% in 6-11 months. 9.7% in 1-2 years old and 14.0% in 2-3years old. Consequently we obtained that the most cases 90.0% were lost their hearing within 3 years after birth. 5) According to qualities of hearing leases the most of cases were perceptive, 197(97.5%), only two cases were conductive, and eight cases were mixed. 6) The status of residual hearing according to average grade of hearing loss. $B(=\frac{a+2b+c}{4}$ as table 13) were as follows. Two cases were normal (one was mute and another was severe speach disorder). Ten cases, moderate. Moderately severe cases were 40 (19.3%). Severe cases, 38(18.4%). Scale out, profound cases, 48 (23.3%). And impossible testing cases because that were infantile or had some mental disorder were 69 (33.3%). 7) The using rate of hearing aides was only 12.0%. Among them who had some more residual hearing and could showed hearing effect with hearing aide have used more many proportionary but who were difficult to expect that effect were rare.