Martsolf syndrome with novel mutation in the TBC1D20 gene in a family from Iran

Abstract

Warburg Micro syndrome and Martsolf syndrome are phenotypically overlapping autosomal recessive conditions characterized by multiple organ abnormalities involving the ocular, nervous, and endocrine systems. Warburg Micro syndrome, the more severe of the two conditions, is caused by loss of function mutations in RAB3GAP1, RAB3GAP2, RAB18, and TBC1D20 genes, whereas Martsolf syndrome has been attributed to less damaging mutations in RAB3GAP1 and RAB3GAP2 genes. We report the clinical description and molecular characterization of a consanguineous Iranian family with two siblings, a male and a female, with dysmorphic features, bilateral congenital cataracts, optic nerve atrophy, congenital glaucoma, mild to moderate intellectual disability, seizures, hypogonadism, and mild osteoporosis. Spastic quadri-

Manifestações orofaciais da lipodistrofia generalizada congênita: uma revisão sistemática

“…Alguns achados faciais menos frequentes observados nos indivíduos com LGC são também observados em diversas síndromes que promovem dismorfismos faciais, tais como linha frontal do cabelo baixa (Elefteriou, et al, 2004;Friguls, et al, 2008), também observada na síndrome de Rubinstein-Taybi (Eser, et al, 2017), síndrome de Cornélia de Lange (Parenti, et al, 2017) e síndrome de Martsolf (Hozhabri, et al, 2020). A presença de hirsutismos localizados é frequente em várias doenças sistêmicas hereditárias, dentre elas a síndrome de Berardinelli-Seip.…”

Micro and Martsolf syndromes in 34 new patients: Refining the phenotypic spectrum and further molecular insights

“…Overall, TBC1D20 mutations were described in five families with Micro syndrome. However, Hozhabri et al reported an Iranian family with Martsolf due to a TBC1D20 mutation providing another evidence of the genetic heterogeneity of the syndrome 14 …”

“…However, the involvement of epigenetic or environmental factors cannot be ruled out. In view of all molecularly defined families with Martsolf, four had mutations in RAB3GAP2 , 3,6,12 two had mutations in RAB3GAP1 , 3,13 and one family had a mutation in TBC1D20 14 . In addition, Gumus reported a family with overlapping features of the two syndromes due to a splice site mutation in RAB3GAP2 gene 11 …”

“…Till now, around 100 families from diverse ethnic groups were molecularly confirmed as Micro syndrome where mutations in RAB3GAP1 were the most common cause (frequency 75%) 3,9,10 . As for Martsolf syndrome, RAB3GAP2 mutations have been described in five families, 3,6,11,12 while RAB3GAP1 and TBC1D20 mutations were found in two and one families, respectively 3,13,14 …”

“…mutations have been described in five families, 3,6,11,12 while RAB3GAP1 and TBC1D20 mutations were found in two and one families, respectively. 3,13,14 In this report, we describe the detailed clinical, neuro-radiological and genetic findings of a large cohort of patients with Micro and Martsolf syndromes.…”