Two novel Warburg micro syndrome 1 cases caused by pathogenic variants in RAB3GAP1

Omid Alavi,Seyed Alireza Dastgheib,Mehdi Dianatpour,Seyed Mehdi Panahandeh,Seyed Mohammad Bagher Tabei,Afrooz Feili,Sina Zoghi,Hossein Jafari Khamirani,Jamal Manoochehri,Majid Kamali

doi:10.1038/s41439-021-00171-9

Abstract

In this study, we detected a novel pathogenic variant and a previously reported variant in RAB3GAP1 by whole-exome sequencing (NM_001172435.2: c.1552C>T, p.Gln518*; c.1471C>T, p.Arg491*). The first patient is a 3-year-old girl who presented with bilateral congenital cataracts, developmental delay, abnormal craniofacial features, drug-resistant constipation, and corpus callosum hypoplasia. The proband of the second family is a 13-year-old boy who suffers from developmental delay, quadriplegia, intellectual disability, abnormal craniofacial features, and corpus callosum hypoplasia.

Highlights

Warburg micro syndrome (WARBM) and Martsolf syndrome are rare genetic disorders caused by a deficiency in RAB18 protein (OMIM: #212720; #600118)
They were regarded as separate entities; later, it was discovered that they are both caused by RAB18 deficiency[1]
Martsolf syndrome is the milder form of RAB18 deficiency, while Warburg micro syndrome is the more severe form

Summary

Introduction

Warburg micro syndrome (WARBM) and Martsolf syndrome are rare genetic disorders caused by a deficiency in RAB18 protein (OMIM: #212720; #600118). Martsolf syndrome is the milder form of RAB18 deficiency, while Warburg micro syndrome is the more severe form. We present two unrelated patients with WARBM1 caused by nonsense pathogenic variants Gln518*; c.1471C>T, p.Arg491*) in RAB3GAP1, the first patients from Iran (Fig. 1A–D).

Results

Conclusion