Clinical and genetic analysis of a child with Niikawa-Kuroki syndrome / 中华医学遗传学杂志

OBJECTIVE@#Clinical examination and molecular genetic analysis were carried out for one case with special facial features with developmental retardation, hearing impairment and cleft lip and palate.@*METHODS@#The intelligence test, hearing test, and MRI test were performed. At the same time, the blood were collected to detect the copy number variation of the whole genome with the chromosomal karyotype analysis and the chromosomal microarray analysis (CMA). And the whole exome sequencing (WES) was used to analyze the pathogenic variant.@*RESULTS@#The children had mild mental retardation and the IQ was 61. There was moderate hearing loss in both ears(left ear 60 dB, right ear 65 dB). And bilateral horizontal hypoplasia of semicircular canal was found by cranial MRI test. No copy number abnormality was found by chromosome karyotype analysis and chromosome microarray analysis in peripheral blood. And whole exome sequencing suggested that there was heterozygous pathogenic variants in KMT2D gene (p.Leu545Argfs*385).@*CONCLUSION@#The patient has a peculiar face and multiple system defects, and was diagnosed as Niikawa-Kuroki syndrome type I by KMT2D gene variant. The whole exome sequencing is helpful for the diagnosis of complex genetic diseases.

Screening for hearing loss and deafness-related genes in newborns / 中华全科医师杂志

To screen the hearing loss and deafness-related genes in newborns,the screenings for hearing loss and the mutations of common deafness-related genes were performed among 8 187 infants born in Shaoxing Maternal and Child Health Care Hospital from August 2013 to November 2014.Twenty mutation spots in deafness-related genes GJB2,GJB3,12SrRNA and SLC26A4 were detected with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).Of 8 187 newborns,hearing loss was confirmed in 10 cases,and mutations in deafness-related genes were detected in 441 cases with a detection rate of 5.39％.Among 441 cases with positive gene mutations,there were 243 cases with GJB2 mutations (2.97％).147 cases with SCL26A4 mutations (1.80％),43 cases with GJB3 mutations (0.53％) and 15 cases with mutations of mitochondrial gene 12SrRNA (0.18％).The spot of highest detection frequency was GJB2 235delC (2.31％),followed by SCL26A4 IVS72A ＞ G (1.31％).The deafness gene detection rate for newborns who did not pass the hearing tests (8.16％,79/968) was higher than these who passed (5.01％,362/7 219;x2 =10.978,P ＜0.05).Five of 10 newborns with hearing loss were detected carrying deafness genes.The detection rate of the common deafness genes among the newborns is relatively high in this region.Screening for hearing loss and deafness gene may contribute to early diagnosis and intervention,and also to long-term precaution for those carrying heterozygosity deafness genes.

Analysis of common mutations of deafness-related genes in 2725 newborns / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen for common mutations of deafness-related genes in order to determine the carrier rate, types of mutation, and their relevance to hearing loss.</p><p><b>METHODS</b>For 4 deafness-related genes GJB2, GJB3, 12S rRNA and SLC26A4, 20 common mutations were screened among 2725 newborns from Shaoxing, Zhejiang by matrix-assisted laser desorption ionization-time of flight-mass spectrometry.</p><p><b>RESULTS</b>Among the 2725 newborns,149 (5.47%) were diagnosed with mutations, which included 84 (3.08%) with GJB2 mutations, 13 (0.48%) with GJB3 mutations, 49 (1.80%) with SLC26A4 mutations and 3 (0.11%) with 12S rRNA mutations. Fourteen mutational hotspots were identified. The most common mutations have included GJB2 c.235delC (65 cases), SLC26A4 IVS7-2A>G (34 cases), GJB2 c.299_300delAT (13 cases), GJB3 c.538C>T (7 cases), GJB2 c.176_191del16 (6 cases) and GJB3 c.547G>A (6 cases).</p><p><b>CONCLUSION</b>The detecting rate for deafness-related gene mutations has been relatively high. To broaden the screening spectrum may improve such rate. Besides GJB2, 12S rRNA, SLC26A4, GJB3 also features a high mutation rate in the region.</p>