Maternally inherited <i>MAF</i> variant associated with variable expression of Aymé‐Gripp syndrome

Alkhunaizi, Ebba; Koenekoop, Robert K.; Saint‐Martin, Christine; Russell, Laura

doi:10.1002/ajmg.a.61299

Cited by 10 publications

(9 citation statements)

References 11 publications

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“…These results are similar to those reported for missense mutations affecting the homologous residues of the transactivation domain of closely related Maf, MafA, and NRL proteins (Fig. 1B) that occur in other disorders (ie, Aymé-Gripp syndrome [AYGRPS], (20,45,46) familial insulinomatosis, (47) and autosomal dominant retinitis pigmentosa [RP27, MIM 613750], (48) respectively). By contrast, heterozygous mutations in MAFB that cause haploinsufficiency or that generate dominant inhibitor proteins lead to the Duane Retraction syndrome-1 (OMIM 126800) that, although not associated with skeletal lesions, does manifest focal segmental glomerulosclerosis.…”

Section: Discussionsupporting

confidence: 88%

Denosumab Treatment Does Not Halt Progression of Bone Lesions in Multicentric Carpotarsal Osteolysis Syndrome

et al. 2023

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Here we report the use of denosumab, a monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), as monotherapy for multicentric carpotarsal osteolysis syndrome (MCTO) in an 11.5-year-old male with a heterozygous missense mutation in MAFB (c.206C>T; p.Ser69Leu). We treated the subject with 0.5 mg/kg denosumab every 60-90 days for 47 months and monitored bone and mineral metabolism, kidney function, joint range of motion (ROM), and bone and joint morphology. Serum markers of bone turnover reduced rapidly, bone density increased, and renal function remained normal. Nevertheless, MCTO-related osteolysis and joint immobility progressed during denosumab treatment. Symptomatic hypercalcemia and protracted hypercalciuria occurred during weaning and after discontinuation of denosumab and required treatment with zoledronate. When expressed in vitro, the c.206C>T; p.Ser69Leu variant had increased protein stability and produced greater transactivation of a luciferase reporter under the control of the PTH gene promoter than did wild-type MafB. Based on our experience and that of others, denosumab does not appear to be efficacious for MCTO and carries a high risk of rebound hypercalcemia and/or hypercalciuria after drug discontinuation.

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Section: Discussionsupporting

confidence: 88%

Denosumab Treatment Does Not Halt Progression of Bone Lesions in Multicentric Carpotarsal Osteolysis Syndrome

et al. 2023

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“…Lastly, a human deletion in GLI3 was associated with causing subclinical autism in the father of a child with ASD and Greig cephalopolysyndactyly syndrome [ 53 ]. Of the upregulated genes, a SZT2 mutation was reported to be causal of a syndrome incorporating autistic features as well as intellectual disability, epilepsy and developmental delay [ 54 ], Serinc2 is a proposed ASD candidate following a chromosomal array [ 55 ] and Maf has variants associated with Aymé-Gripp syndrome, which includes ASD as a characteristic [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Brain Gene Expression Data from Mouse Model Studies of Maternal Immune Activation Using Poly(I:C)

Laighneach

Desbonnet

Kelly

et al. 2021

Genes

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Maternal immune activation (MIA) is a known risk factor for schizophrenia (SCZ) and autism spectrum disorder (ASD) and is often modelled in animal studies in order to study the effect of prenatal infection on brain function including behaviour and gene expression. Although the effect of MIA on gene expression are highly heterogeneous, combining data from multiple gene expression studies in a robust method may shed light on the true underlying biological effects caused by MIA and this could inform studies of SCZ and ASD. This study combined four RNA-seq and microarray datasets in an overlap analysis and ranked meta-analysis in order to investigate genes, pathways and cell types dysregulated in the MIA mouse models. Genes linked to SCZ and ASD and crucial in neurodevelopmental processes including neural tube folding, regulation of cellular stress and neuronal/glial cell differentiation were among the most consistently dysregulated in these ranked analyses. Gene ontologies including K+ ion channel function, neuron and glial cell differentiation, synaptic structure, axonal outgrowth, cilia function and lipid metabolism were also strongly implicated. Single-cell analysis identified excitatory and inhibitory cell types in the cortex, hippocampus and striatum that may be affected by MIA and are also enriched for genes associated with SCZ, ASD and cognitive phenotypes. This points to the cellular location of molecular mechanisms that may be consistent between the MIA model and neurodevelopmental disease, improving our understanding of its utility to study prenatal infection as an environmental stressor.

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“…Dominant pathogenic variants of MAF (MIM# 601088) are associated with Aymé-Gripp syndrome, a condition presenting with mild to severe intellectual disability syndrome, autism spectrum disorder, cataracts, short stature, seizures, and skeletal involvement. To date, there were only two adult cases of Aymé-Gripp syndrome present late-onset renal disease (25,26). It has been reported a 43-year-old patient with the same variant of MAF (p.Ser54Leu) presented with proteinuria and typical clinical features of Aymé-Gripp syndrome, subsequently diagnosed with mesangiocapillary glomerulopathy (26).…”

Section: Discussionmentioning

confidence: 99%

Characteristics and outcomes of glomerulonephritis with membranoproliferative pattern in children

Xu¹,

Wei²,

Feng³

et al. 2021

Transl Pediatr

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Background: Membranoproliferative glomerulonephritis (MPGN) is a rare histopathologic pattern of glomerular injury with limited studies in pediatric patients. Characteristics and outcomes of children with MPGN have also remained to be further explored. Methods:We retrospectively reviewed the clinicopathological features, genetic findings, treatments and outcomes in 17 pediatric patients pathologically diagnosed with MPGN from 2007 to 2020 in the Children's National Medical Center in China.Results: Median age at disease onset was 9.9 years (IQR, 5.6-11.9 years). Most of the patients (12/17) had nephrotic range of proteinuria, and nephritic-nephrotic syndrome was the most common clinical presentation (35.2%). Secondary causes were identified in eight patients including hepatitis B virus (HBV) infection (n=4), methylmalonic acidemia (MMA, n=2), rheumatoid arthritis (RA, n=1) and Aymé-Gripp Syndrome (n=1). The nine patients with primary MPGN were further identified as immune-complex mediated MPGN (n=8), and unclassifiable MPGN (U-MGPN, n=1). Genetic analyses identified pathogenic variants of MMACHC gene in two cases of MMA and established the diagnosis for Aymé-Gripp syndrome in one case with a de novo variant of MAF gene. Comparing study between the complete or partial remission group (n=8) and non-response group (n=9) showed a significant difference in the timing of renal biopsy (P<0.05). Normal renal function was preserved in ten patients at the last follow-up. Two patients developed into end-stage renal disease (ESRD). Conclusions:Children with MPGN pattern present heterogenous clinical features. Genetic detection helps to explore underlying causes of MPGN. Early identification of the primary or secondary causes of MPGN in children is vital.

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Maternally inherited MAF variant associated with variable expression of Aymé‐Gripp syndrome

Cited by 10 publications

References 11 publications

Denosumab Treatment Does Not Halt Progression of Bone Lesions in Multicentric Carpotarsal Osteolysis Syndrome

Denosumab Treatment Does Not Halt Progression of Bone Lesions in Multicentric Carpotarsal Osteolysis Syndrome

Meta-Analysis of Brain Gene Expression Data from Mouse Model Studies of Maternal Immune Activation Using Poly(I:C)

Characteristics and outcomes of glomerulonephritis with membranoproliferative pattern in children

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