Biallelic Splicing Variant c.12479+ <scp>3A</scp> >G in <i>FAT4</i> Causes Hennekam Lymphangiectasia‐Lymphedema Syndrome 2
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.
Authors
- Selinda Mascarenhas
- Katta M. Girisha
- Periyasamy Radhakrishnan (ORCID: https://orcid.org/0000-0002-7690-3201)
- Shruti Pande
- Anju Shukla
- Huzail Shaikh
- Akhil K. A.
- Yashavi Gupta
Institutions
- Manipal Academy of Higher Education (IN)
- University Hospital of Basel (CH)
- Department of Biomedicine Basel (CH)
- Sultan Qaboos University (OM)
- Kasturba Medical College, Manipal (IN)
Publication Details
- Journal
- American Journal of Medical Genetics Part A
- Published
- 2026-04-16
- DOI
- https://doi.org/10.1002/ajmg.a.70166
- Primary Topic
- Lymphatic System and Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- The Wellcome Trust DBT India Alliance