Martsolf Syndrome

Last update 01 Nov 2024

Basic Info

Synonyms

CATARACT-MENTAL RETARDATION-HYPOGONADISM, Cataract, mental retardation, hypogonadism, Cataract-Mental Retardation-Hypogonadism

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Introduction

Syndrome with the association of intellectual deficit, congenital cataract, and hypogonadotropic hypogonadism. Less than 20 cases have been described in the literature so far. Besides the three main features of the syndrome, other anomalies have been reported in some of the affected patients including short stature, minor digital abnormalities, microcephaly, cardiomyopathy, heart failure, and mild facial dysmorphism (micrognathia, maxilla hypoplasia, low posterior hairline and large ears). Mutations in the RAB3GAP2 gene have been identified in some patients. Transmission is autosomal recessive.

100 Clinical Results associated with Martsolf Syndrome

100 Translational Medicine associated with Martsolf Syndrome

0 Patents (Medical) associated with Martsolf Syndrome

Literatures (Medical) associated with Martsolf Syndrome

01 Dec 2021·BMC NeurologyQ4 · MEDICINE

Novel manifestations of Warburg micro syndrome type 1 caused by a new splicing variant of RAB3GAP1: a case report

Q4 · MEDICINE

ArticleOA

Author: Khalesi, Raziyeh ; Riazalhosseini, Yasser ; Razmara, Ehsan ; Auld, Daniel ; Asgaritarghi, Golareh ; Garshasbi, Masoud ; Tavasoli, Ali Reza

AbstractBackgroundThe present study aimed to determine the underlying genetic factors causing the possible Warburg micro syndrome (WARBM) phenotype in two Iranian patients.Case presentationA 5-year-old female and a 4.5-year-old male were referred due to microcephaly, global developmental delay, and dysmorphic features. After doing neuroimaging and clinical examinations, due to the heterogeneity of neurodevelopmental disorders, we subjected 7 family members to whole-exome sequencing. Three candidate variants were confirmed by Sanger sequencing and allele frequency of each variant was also determined in 300 healthy ethnically matched people using the tetra-primer amplification refractory mutation system-PCR and PCR-restriction fragment length polymorphism. To show the splicing effects, reverse transcription-PCR (RT-PCR) and RT-qPCR were performed, followed by Sanger sequencing. A novel homozygous variant—NM_012233.2: c.151-5 T > G; p.(Gly51IlefsTer15)—in the RAB3GAP1 gene was identified as the most likely disease-causing variant. RT-PCR/RT-qPCR showed that this variant can activate a cryptic site of splicing in intron 3, changing the splicing and gene expression processes. We also identified some novel manifestations in association with WARBM type 1 to touch upon abnormal philtrum, prominent antitragus, downturned corners of the mouth, malaligned teeth, scrotal hypoplasia, low anterior hairline, hypertrichosis of upper back, spastic diplegia to quadriplegia, and cerebral white matter signal changes.ConclusionsDue to the common phenotypes between WARBMs and Martsolf syndrome (MIM: 212720), we suggest using the “RABopathies” term that can in turn cover a broad range of manifestations. This study can per se increase the genotype-phenotype spectrum of WARBM type 1.

01 Nov 2020·Clinical GeneticsQ2 · MEDICINE

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

Q2 · MEDICINE

Review

Author: Effat, Laila K. ; Abdel‐Hamid, Mohamed S. ; Desouky, Lubna M. ; Issa, Mahmoud Y. ; Ismail, Suzan R. ; Zaki, Maha S. ; Abdel‐Ghafar, Sherif F.

AbstractMicro and Martsolf syndromes are rare clinically and genetically overlapping disorders caused by mutations in RAB3GAP1, RAB3GAP2, RAB18 and TBC1D20 genes. We describe 34 new patients, 27 with Micro and seven with Martsolf. Patients presented with the characteristic clinical manifestations of the two syndromes, including postnatal microcephaly, congenital cataracts, microphthalmia, optic atrophy, spasticity and intellectual disability. Brain imaging showed in the majority of cases polymicrogyria, thin corpus callosum, cortical atrophy, and white matter dysmyelination. Unusual additional findings were pectus excavatum (four patients), pectus carinatum (three patients), congenital heart disease (three patients) and bilateral calcification in basal ganglia (one patient). Mutational analysis of RAB3GAP1 and RAB3GAP2 revealed 21 mutations, including 14 novel variants. RAB3GAP1 mutations were identified in 22 patients with Micro, including a deletion of the entire gene in one patient. On the other hand, RAB3GAP2 mutations were identified in two patients with Micro and all Martsolf patients. Moreover, exome sequencing unraveled a TBC1D20 mutation in an additional family with Micro syndrome. Our results expand the phenotypic and mutational spectrum associated with Micro and Martsolf syndromes. Due to the overlapped severities and genetic basis of both syndromes, we suggest to be comprehended as one entity “Micro/Martsolf spectrum” or “RAB18 deficiency.”

01 Jun 2020·Molecular Case Studies

Hypogonadotropic hypogonadism due to variants in RAB3GAP2: expanding the phenotypic and genotypic spectrum of Martsolf syndrome

Review

Author: Swords, Francesca ; Plummer, Lacey ; Crowley, William F ; Xu, Wanxue ; Seminara, Stephanie B ; Balasubramanian, Ravikumar ; Quinton, Richard

Biallelic pathogenic variants in RAB3GAP2 cause Warburg Micro syndrome (WARBM) and Martsolf syndrome (MS), two rare, phenotypically overlapping disorders characterized by congenital cataracts, intellectual disability, and hypogonadism. Although the initial report documented hypergonadotropic hypogonadism (implying a gonadal defect), an adolescent girl with WARBM/MS was subsequently reported to have hypogonadotropic hypogonadism (implying a central defect in either the hypothalamus or anterior pituitary). However, in adult MS, hypogonadotropism has not been convincingly demonstrated. Additionally, the correlation between the pathogenic severity of variants in RAB3GAP2 and the phenotypic severity also remains unclear. Here we present a clinical report of a woman with congenital cataracts, apparent intellectual disability, and pubertal failure who underwent exome sequencing (ES) to determine a precise molecular diagnosis. Reproductive phenotypes reported previously in individuals with MS and the genotypic spectrum of previous RAB3GAP2 variants were also reviewed. The ES identified pathogenic compound heterozygous RAB3GAP2 variants (c.387-2A > G; p.(Arg428Glu)) combined with her phenotypic features, which enabled a unifying molecular diagnosis of MS. Reproductive evaluation confirmed a normosmic idiopathic hypogonadotropic hypogonadism. Review of the RAB3GAP2 allelic spectrum in WARBM/MS suggests that although variants resulting in complete abrogation of RAB3GAP2 protein function cause severe WARBM, variants associated with partially preserved RAB3GAP2 function cause milder MS. This report expands the genotypic and phenotypic spectrum of MS and demonstrates hypogonadotropic hypogonadism as a key pathophysiologic abnormality in MS. Genotype–phenotype associations of previously reported RAB3GAP2 variants indicate that variants that fully abolish RAB3GAP2 function result in WARBM, whereas MS is associated with variants of lesser severity with residual RAB3GAP2 function.

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Martsolf Syndrome

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