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 (NM₀01291303. 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.
Mascarenhas et al. (Thu,) studied this question.