Kabuki syndrome

McVeigh, Terri P; Banka, Siddharth; Reardon, William

doi:10.1097/mcd.0000000000000092

Cited by 23 publications

(6 citation statements)

References 41 publications

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“…In this case, surgical Microphthalmia was described in several KS patients. In one neonate, extreme microphthalmia with an anomaly of globe development, hyperplastic primary vitreous and hypoplastic optic chiasm were all present [136]. KMT2D variant was later confirmed in this patient.…”

Section: Ophthalmologic Issues In Kabuki Syndromesupporting

confidence: 52%

“…Additionally, KMT2D has been known to interact with the PAX-interacting protein 1 (PAXIP-1) as well as other transcription factors encoded by PAX2. These factors have a high rate of expression in the developing eye, which may also explain microphthalmia and eye developmental disorder in utero [136]. Ocular muscle dysfunction was recently reported.…”

Section: Ophthalmologic Issues In Kabuki Syndromementioning

confidence: 99%

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Kabuki Syndrome—Clinical Review with Molecular Aspects

Boniel

Sztefko

Śmigiel

et al. 2021

Genes

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Kabuki syndrome (KS) is a rare developmental disorder principally comprised of developmental delay, hypotonia and a clearly defined dysmorphism: elongation of the structures surrounding the eyes, a shortened and depressed nose, thinning of the upper lip and thickening of the lower lip, large and prominent ears, hypertrichosis and scoliosis. Other characteristics include poor physical growth, cardiac, gastrointestinal and renal anomalies as well as variable behavioral issues, including autistic features. De novo or inherited pathogenic/likely pathogenic variants in the KMT2D gene are the most common cause of KS and account for up to 75% of patients. Variants in KDM6A cause up to 5% of cases (X-linked dominant inheritance), while the etiology of about 20% of cases remains unknown. Current KS diagnostic criteria include hypotonia during infancy, developmental delay and/or intellectual disability, typical dysmorphism and confirmed pathogenic/likely pathogenic variant in KMT2D or KDM6A. Care for KS patients includes the control of physical and psychomotor development during childhood, rehabilitation and multi-specialist care. This paper reviews the current clinical knowledge, provides molecular and scientific links and sheds light on the treatment of Kabuki syndrome individuals.

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Section: Ophthalmologic Issues In Kabuki Syndromesupporting

confidence: 52%

Section: Ophthalmologic Issues In Kabuki Syndromementioning

confidence: 99%

Kabuki Syndrome—Clinical Review with Molecular Aspects

Boniel

Sztefko

Śmigiel

et al. 2021

Genes

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“…Notably, KMT2D and PAXIP1 are closely related functionally, as they are part of the same functional complex, interacting physically ( 47 ), and mutations in either one of the two proteins can cause one same disease, i.e. Kabuki syndrome ( 48 ). Interestingly, heptad-spaced hydrophobic residues (mostly leucine) were interspersed in the polyQ repeats of both proteins, consistent with the formation of stabilized polyQ CC interfaces ( 1 , 10 ).…”

Section: Resultsmentioning

confidence: 99%

PolyQ length co-evolution in neural proteins

Vaglietti

Fiumara

2021

NAR Genomics and Bioinformatics

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Intermolecular co-evolution optimizes physiological performance in functionally related proteins, ultimately increasing molecular co-adaptation and evolutionary fitness. Polyglutamine (polyQ) repeats, which are over-represented in nervous system-related proteins, are increasingly recognized as length-dependent regulators of protein function and interactions, and their length variation contributes to intraspecific phenotypic variability and interspecific divergence. However, it is unclear whether polyQ repeat lengths evolve independently in each protein or rather co-evolve across functionally related protein pairs and networks, as in an integrated regulatory system. To address this issue, we investigated here the length evolution and co-evolution of polyQ repeats in clusters of functionally related and physically interacting neural proteins in Primates. We observed function-/disease-related polyQ repeat enrichment and evolutionary hypervariability in specific neural protein clusters, particularly in the neurocognitive and neuropsychiatric domains. Notably, these analyses detected extensive patterns of intermolecular polyQ length co-evolution in pairs and clusters of functionally related, physically interacting proteins. Moreover, they revealed both direct and inverse polyQ length co-variation in protein pairs, together with complex patterns of coordinated repeat variation in entire polyQ protein sets. These findings uncover a whole system of co-evolving polyQ repeats in neural proteins with direct implications for understanding polyQ-dependent phenotypic variability, neurocognitive evolution and neuropsychiatric disease pathogenesis.

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“…Furthermore, Paxip1 is expressed in the branchial arches of mouse embryos (Fowles et al, 2003), and is intolerant to missense variation (Constraint Score = 3.28; Table S10). Interestingly, PAXIP1 is associated with Kabuki syndrome, a disorder whose phenotypic spectrum includes OFC (McVeigh et al, 2015). To clarify whether the identified susceptibility genes make a true contribution to ns-CL/P, functional studies are warranted using in vivo models suitable for the investigation of craniofacial development.…”

Section: Discussionmentioning

confidence: 99%

Identification of de novo variants in nonsyndromic cleft lip with/without cleft palate patients with low polygenic risk scores

Ishorst

Henschel

Thieme

et al. 2022

Molec Gen & Gen Med

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Background: Nonsyndromic cleft lip with/without cleft palate (nsCL/P) is a congenital malformation of multifactorial etiology. Research has identified >40 genome-wide significant risk loci, which explain less than 40% of nsCL/P heritability. Studies show that some of the hidden heritability is explained by rare penetrant variants. Methods:To identify new candidate genes, we searched for highly penetrant de novo variants (DNVs) in 50 nsCL/P patient/parent-trios with a low polygenic risk for the phenotype (discovery).We prioritized DNV-carrying candidate genes from the discovery for resequencing in independent cohorts of 1010 nsCL/P patients of diverse ethnicities and 1574 population-matched controls (replication). Segregation analyses and rare

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Kabuki syndrome

Cited by 23 publications

References 41 publications

Kabuki Syndrome—Clinical Review with Molecular Aspects

Kabuki Syndrome—Clinical Review with Molecular Aspects

PolyQ length co-evolution in neural proteins

Identification of de novo variants in nonsyndromic cleft lip with/without cleft palate patients with low polygenic risk scores

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