3-M Syndrome: A Local Case Report

Habibullah, Hafiz; Albaradie, Raidah; Bashir, Shahid

doi:10.12659/ajcr.912736

Cited by 5 publications

(5 citation statements)

References 6 publications

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“…Among them, 19 resulted in early termination of translation, and 6 of which led to missense mutations 8 , 46 . Recently, several novel CUL7 mutations have been discovered in 3-M syndrome, expanding our knowledge of phenotype-genotype correlations in this disease 47 – 49 . Moreover, Maksimova proposed that a founder chromosome responsible for the CUL7 mutation also exists in Yakuts short stature syndrome 9 .…”

Section: Physiological and Pathological Effects Of The Cul7 E3 Ligasementioning

confidence: 99%

The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer

Shi¹,

Du²,

Peng³

et al. 2020

Oncogenesis

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Cullin (CUL) proteins have critical roles in development and cancer, however few studies on CUL7 have been reported due to its characteristic molecular structure. CUL7 forms a complex with the ROC1 ring finger protein, and only two F-box proteins Fbxw8 and Fbxw11 have been shown to bind to CUL7. Interestingly, CUL7 can interact with its substrates by forming a novel complex that is independent of these two F-box proteins. The biological implications of CUL-ring ligase 7 (CRL7) suggest that the CRL7 may not only perform a proteolytic function but may also play a non-proteolytic role. Among the existing studied CRL7-based E3 ligases, CUL7 exerts both tumor promotion and suppression in a context-dependent manner. Currently, the mechanism of CUL7 in cancer remains unclear, and no studies have addressed potential therapies targeting CUL7. Consistent with the roles of the various CRL7 adaptors exhibit, targeting CRL7 might be an effective strategy for cancer prevention and treatment. We systematically describe the recent major advances in understanding the role of the CUL7 E3 ligase in cancer and further summarize its potential use in clinical therapy.

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Section: Physiological and Pathological Effects Of The Cul7 E3 Ligasementioning

confidence: 99%

The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer

Shi¹,

Du²,

Peng³

et al. 2020

Oncogenesis

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“…During the investigation of developmental delay, cranial MRI revealed cerebellar atrophy with brain stem and supratentorial volume loss [HabibUllah et al, 2019]. Interestingly, the present patient had GDD, and the diagnosis of 3M syndrome was not considered as a differential diagnosis in her previous admissions before her referral to our center.…”

Section: Discussionmentioning

confidence: 67%

Typical Face, Developmental Delay, and Hearing Loss in a Patient with 3M Syndrome: The Co-Occurrence of Two Rare Conditions

et al. 2022

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Introduction: 3M syndrome is an autosomal recessive disorder characterized by characteristic facial features, severe pre- and postnatal growth restriction (<–4 SDS), and normal mental development. 3M syndrome is genetically heterogeneous. Up to date, causative mutations have been demonstrated in 3 genes, cullin-7 (CUL7), obscurin-like 1 (OBSL1), and coiled coil domain containing protein 8 (CCDC8). Case presentation: Here, we report a patient who was referred to our clinic due to short stature and developmental delay. Physical examination revealed prenatal onset short stature, low birth weight, and normal head circumference. She displayed several dysmorphic facial features in addition to developmental delay and bilateral sensorineural hearing loss. The physical findings were suggestive of 3M syndrome. Genetic assessment revealed a novel homozygous frameshift c.418_419delAC (p.Thr140Cysfs*11) variant in the CUL7 gene and a previously reported pathogenic nonsense homozygous c.942C>A (p.Cys314Ter) variant in the ILDR1 gene. The parents were heterozygous for the same variant. Discussion: 3M syndrome should be considered in the differential diagnosis of patients with short stature and typical facial features even if in the presence of other inconsistent features such as developmental delay. In addition, it is important to take into account the co-occurrence of rare autosomal recessive genetic disorders especially in countries with a high consanguineous marriage rate.

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“…As one of the affected individuals (401) had low IQ which is not a characteristic of 3M2, we launched a search in his exome file for a homozygous candidate variant which could underlie the trait (Appendix A: Supplementary Material). Having not found any good candidate, we hypothesized that low IQ could be a rare, variable finding in 3M2, considering that another case has been reported with mild ID [ 4 ].…”

Section: Resultsmentioning

confidence: 99%

“…Three M Syndrome (3MS) is an extremely rare disorder with autosomal recessive inheritance [ 4 ]. Miller et al (1975) described two siblings born to first-cousin parents who had low birth weight, short stature, narrow facies, grooved lower anterior thorax, and clinodactyly, and the disorder was named 3MS after the shared initial of the describing researchers: Miller, McKusick, and Malvaux [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Additional variable musculoskeletal findings reported include short neck, square shoulders, short thorax, thin ribs, lumbar hyperlordosis, winged scapulae, small narrow pelvis, joint hypermobility, pes planus, and prominent heels [ 7 ]. Intelligence is reported to be normal in all cases except for one case with mild intellectual disability (ID) [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Expanding OBSL1 Mutation Phenotype: Disproportionate Short Stature, Barrel Chest, Thoracic Kyphoscoliosis, Hypogonadism, and Hypospadias

Koprulu,

Shabbir,

Mumtaz

et al. 2023

Yale J Biol Med

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We present a Pakistani kinship afflicted with a syndrome with features including short stature, reduced sitting height, orofacial symptoms including prominent forehead and thick eyebrows, short and broad thorax, and variable features such as long philtrum, short broad neck, barrel chest, thoracic kyphoscoliosis, hypogonadism, and hypospadias. Phenotypic variation even within different sibships was considerable. The unique combination of the phenotypic characteristics prompted us to determine the shared homozygosity regions in patient genomes and the pathogenic variants by next generation technologies like single nucleotide polymorphism (SNP) genotyping and whole exome sequencing (WES). Through these analyses, we detected homozygous OBSL1 c.848delG (p.Gly283AlafsTer54) as the causal variant. Biallelic variants in OBSL1 are known to cause Three M Syndrome 2 (3M2), a rare disorder of growth retardation with characteristic facial dysmorphism and musculoskeletal abnormalities. Affected members of the family do not have the 3M2 hallmark features of dolichocephaly, hypoplastic midface, anteverted nares, low nasal bridge, pectus excavatum, sacral hyperlordosis, spina bifida occulta, anterior wedging of thoracic vertebrae, prominent heels, and prominent talus. Moreover, they have some variable features not typical for the syndrome such as round face, disproportionate short stature, barrel chest, thoracic kyphoscoliosis, hypogonadism, and hypospadias. Our study facilitated genetic diagnosis in the family, expanded the clinical phenotype for 3M2, and unraveled the considerable clinical variation within the same kinship. We conclude that unbiased molecular analyses such as WES should be more integrated into healthcare, particularly in populations with high parental consanguinity, given the potential of such analyses to facilitate diagnosis.

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3-M Syndrome: A Local Case Report

Cited by 5 publications

References 6 publications

The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer

The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer

Typical Face, Developmental Delay, and Hearing Loss in a Patient with 3M Syndrome: The Co-Occurrence of Two Rare Conditions

Expanding OBSL1 Mutation Phenotype: Disproportionate Short Stature, Barrel Chest, Thoracic Kyphoscoliosis, Hypogonadism, and Hypospadias

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