Identification of VEGFR3 gene mutation in a Chinese family with autosomal dominant primary congenital lymphoedema / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the disease-causing gene in a four-generation Chinese family with 9 members affected with primary congenital lymphoedema (PCL, also known as Milroy disease).</p><p><b>METHODS</b>Linkage analysis was performed with a few microsatellite markers flanking the candidate genetic loci for PCL, including 3 known genes associated with autosomal dominant PCL. For mutation analysis, VEGFR3 gene was sequenced with DNA from the proband. Direct DNA sequencing of exon 25 of the VEGFR3 gene was performed in all family members.</p><p><b>RESULTS</b>The disease gene in the family was mapped to chromosome 5q35.3 with a maximum Lod score of 2.07. Direct DNA sequencing of VEGFR3 gene revealed a heterozygous C to T transition at nucleotide 3341, resulting in p.Pro1114Leu mutation. The p.Pro1114Leu mutation co-segregated with all affected individuals in the family.</p><p><b>CONCLUSION</b>This study identified a C3341T (p.Pro1114Leu) mutation in the VEGFR3 gene in a Chinese family with PCL, provided evidence that VEGFR3 mutation can cause PCL in Chinese.</p>

c.359T>C mutation of the MYH14 gene in two autosomal dominant non-syndromic hearing impairment families with common ancestor / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the gene mutation for two Chinese families with autosomal dominant non-syndromic hearing impairment(NSHI).</p><p><b>METHODS</b>Two NSHI pedigrees with common ancestor were identified by clinical examination and family investigation. Linkage analysis was performed for all known NSHI loci, and all exons and exon-intron boundaries of the non-muscle myosin heavy chain 14 (MYH14) gene were amplified by PCR and sequenced.</p><p><b>RESULTS</b>The disease-causing gene of these 2 pedigrees was fine mapped to the DFNA4 locus on 19q13.33. A heterozygous transition of c. 359T>C (p.S120L) in MYH14 gene was identified. The mutation was detected in all patients but not in normal members in the two families.</p><p><b>CONCLUSION</b>It is the first report that mutation in MYH14 gene can cause dominant non-syndromic hearing impairment in Asian population, suggesting that MYH14 gene can be a disease-causing gene of Chinese patients with hearing impairment.</p>

Two novel missense mutations of GATA4 gene in Chinese patients with sporadic congenital heart defects / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify mutations in GATA4 gene in Chinese patients with sporadic congenital heart defects (CHD).</p><p><b>METHODS</b>Single stranded conformation polymorphism (SSCP) analysis was performed to screen for mutations in all six exons and exon-intron boundaries of GATA4 in 31 individuals with CHD. Direct DNA sequencing was used to identify the specific mutations.</p><p><b>RESULTS</b>Two novel missense mutations, V267M in exon 4, V380M in exon 6, and one polymorphism in intron 6 of GATA4 were identified.</p><p><b>CONCLUSION</b>The above identified two novel GATA4 mutations associated with CHD in Chinese patients. This suggests that the transcription factor GATA4 may play an important role in cardiogenesis.</p>

The G401D mutation of OPA1 causes autosomal dominant optic atrophy and hearing loss in a Chinese family / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To describe the clinical and genetic characteristics of a Chinese family affected with optic atrophy 1 (OPA1).</p><p><b>METHODS</b>Linkage analysis and DNA sequencing as well as PCR/restriction fragment length polymorphism (RFLP) analysis were performed to identify the disease-causing mutation.</p><p><b>RESULTS</b>A missense mutation, G401D in the OPA1 gene was identified, and the patients demonstrate inherited syndrome of optic atrophy and hearing loss.</p><p><b>CONCLUSION</b>The present study demonstrates that a mutation in the OPA1 gene can cause optic atrophy in Chinese patients, and supports the notion that OPA1 mutation may lead to OPA1 combined with hearing loss.</p>

Advances in the studies on the molecular and genetic aspects of epilepsy / 中国医学科学院学报

Epilepsy is one of the most common and debilitating neurological diseases that affects more than 40 million people worldwide. Genetic factors contribute to the pathogenesis of epilepsy. Molecular genetic studies have identified 15 disease-causing genes for epilepsy. The majority of the genes encode ion channels, including voltage-gated potassium channels KCNQ2 and KCNQ3, sodium channels SCN1A, SCN2A, and SCN1B, chloride channels CLCN2, and ligand-gated ion channels CHRNA4, CHRNB2, GABRG2, and GABRA1. Interestingly, non-ion channel genes have also been identified as epilepsy genes, and these genes include G-protein-coupled receptor MASS1/VLGR1, GM3 synthase, and proteins with unknown functions such as LGI1, NHLRC1, and EFHC1. These studies make genetic testing possible in some patients, and further characterization of the identified epilepsy genes may lead to the development of new drugs and new treatments for patients with epilepsy.