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Published on: October 9, 2014
Biallelic Splicing Variant c.12479+3A>G in FAT4 Causes Hennekam Lymphangiectasia-Lymphedema Syndrome 2
Selinda Mascarenhas1, Yashavi Gupta1, Akhil K A1
1Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India.
Abstract:
Hennekam lymphangiectasia-lymphedema syndrome (HKLLS) is an autosomal recessive disorder, caused by biallelic variants in CCBE1, FAT4, and ADAMTS3 genes. We herein report a 15-month-old male with peripheral lymphedema, facial dysmorphism, camptodactyly and generalized hypotonia. Solo exome sequencing revealed a homozygous splice site variant, c.12479+3A>G in intron 14 of FAT4 (NM_001291303.3). Reverse transcriptase-PCR (RT-PCR) was performed using cDNA isolated from patient-derived fibroblasts, which revealed aberrant splicing. This study provides a report of an additional family with a novel biallelic splice site variant in FAT4 which disrupts the normal splicing of the FAT4 mRNA, leading to aberrant splicing causing a milder form of HKLLS2.
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