Microvillus Inclusion Disease Variant in an Infant with Intractable Diarrhea

Alsaleem, Badr; Ahmed, Amna Basheer M.; Fageeh, Musa

doi:10.1159/000479624

Cited by 15 publications

(13 citation statements)

References 18 publications

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“…600876). 1,[6][7][8][9]12 These include a homozygous nonsense mutation (c.739C > T, p.Arg247 Ã , Ensembl COSM193004) in exon 9 and a homozygous frame-shifting 2-bp insertion (c.372_373dup, p.Arg125Leufs Ã 7) in exon 6 of STX3. Both mutations were predicted to cause cellular STX3 protein depletion and truncation.…”

Section: Discussionmentioning

confidence: 99%

Microvillus Inclusion Disease: A Rare Mutation of STX3 in Exon 9 Causing Fatal Congenital Diarrheal Disease

et al. 2020

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Inherited diarrheal disorders cause serious morbidity resulting in dependence on intensive care and parenteral nutrition. Microvillus inclusion disease (MVID) has been classically described and results from mutations in the gene coding myosin Vb, which is responsible for enterocyte polarization. Newer reports of mutations resulting in truncated syntaxin 3 (STX3) and Munc18-2 (STXBP2) proteins have been elucidated as causative. To date, five cases of STX3 abnormalities resulting in MVID have been described. We report an infant who presented with congenital diarrhea and was determined to have a rare mutation of STX3. This new finding would be beneficial in future functional genotype–phenotype correlation studies.

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Section: Discussionmentioning

confidence: 99%

Microvillus Inclusion Disease: A Rare Mutation of STX3 in Exon 9 Causing Fatal Congenital Diarrheal Disease

et al. 2020

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“…Our patient has a c.1462del that has not been reported in literature as a cause of MVID. Mutations in Syntaxin 3 have been reported as causes for atypical, milder form of MVID[9,10]. Syntaxin 3 is an apical SNARE receptor protein necessary for microvilli-lined vesicular docking.…”

Section: Discussionmentioning

confidence: 99%

“…Syntaxin 3 is an apical SNARE receptor protein necessary for microvilli-lined vesicular docking. Histological features in the atypical variant are the same with the exception of location of secretory granules, which are located along the basolateral membrane and microvilli at the lateral surfaces[9,10]. Decreased expression of sodium hydrogen exchanger, sodium glucose co-transporter leads to impaired water absorption, while expression of cystic fibrosis transmembrane conductance regulator leads to chloride secretion and accounts for high losses of sodium and chloride[11,12].…”

Section: Discussionmentioning

confidence: 99%

Congenital diarrhea in a newborn infant: A case report

Sadiq

Choudry

Kashyap

et al. 2019

WJCP

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BACKGROUNDMicrovillus inclusion disease (MVID) is a rare autosomal recessive cause of severe congenital diarrhea with significant morbidity and mortality. Definitive treatment involves bowel transplant. The diagnosis of this condition can be challenging and a few genetic panels are available for the identification of the most common mutations. We present the case of an infant with MVID due to a mutation not reported in the literature before.CASE SUMMARYWe report the case of an infant transferred to our institution with severe diarrhea of unknown etiology, failure to thrive, and significant metabolic derangements. An extensive work-up including stool studies for common gastrointestinal pathogens, abdominal ultrasound, esophagogastroduodenoscopy with duodenal biopsy and flexible sigmoidoscopy failed to reveal a diagnosis. Multiple dietary and formula regimens were introduced but all resulted in voluminous diarrhea. She remained on total parenteral nutrition (TPN) for the duration of her hospital stay. Genetic testing was done and she was subsequently found to have a novel mutation in the MYO5B gene [homozygous mutation for MYO5B c.1462del, p. (Ile488Leufs*93)] giving us the diagnosis of MVID. She remains on TPN while awaiting bowel transplant at the time of the compilation of this case report.CONCLUSIONWe report a novel mutation involved in MVID and highlight the importance of considering this disease when faced with a newborn presenting with life threatening diarrhea. At the time of this publication, 232 allelic variations of this gene (MIM#606540) exist in National Center for Biotechnology Information’s database. Our patient’s mutation has not been reported in literature as a cause of MVID.

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“…The disease pathology fundamentally resulted from a loss of polarized apical transport, apical atrophy of enterocyte apical microvilli as well as intracellular accumulation of apical enzymes and microvillus‐like structures under transmission electron microscopy. Variants of MVID have been recognized to result from MUNC18‐2 (Dhekne et al, 2018; Vogel et al, 2017) and homozygous mutations in STX3 (Alsaleem et al, 2017; Julia et al, 2019; Wiegerinck et al, 2014).…”

Section: Other Snare‐associated Developmental Disordersmentioning

confidence: 99%

SNAREs and developmental disorders

Tang

2020

Journal Cellular Physiology

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Members of the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) family mediate membrane fusion processes associated with vesicular trafficking and autophagy. SNAREs mediate core membrane fusion processes essential for all cells, but some SNAREs serve cell/tissue type‐specific exocytic/endocytic functions, and are therefore critical for various aspects of embryonic development. Mutations or variants of their encoding genes could give rise to developmental disorders, such as those affecting the nervous system and immune system in humans. Mutations to components in the canonical synaptic vesicle fusion SNARE complex (VAMP2, STX1A/B, and SNAP25) and a key regulator of SNARE complex formation MUNC18‐1, produce variant phenotypes of autism, intellectual disability, movement disorders, and epilepsy. STX11 and MUNC18‐2 mutations underlie 2 subtypes of familial hemophagocytic lymphohistiocytosis. STX3 mutations contribute to variant microvillus inclusion disease. Chromosomal microdeletions involving STX16 play a role in pseudohypoparathyroidism type IB associated with abnormal imprinting of the GNAS complex locus. In this short review, I discuss these and other SNARE gene mutations and variants that are known to be associated with a variety developmental disorders, with a focus on their underlying cellular and molecular pathological basis deciphered through disease modeling. Possible pathogenic potentials of other SNAREs whose variants could be disease predisposing are also speculated upon.

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Microvillus Inclusion Disease Variant in an Infant with Intractable Diarrhea

Cited by 15 publications

References 18 publications

Microvillus Inclusion Disease: A Rare Mutation of STX3 in Exon 9 Causing Fatal Congenital Diarrheal Disease

Microvillus Inclusion Disease: A Rare Mutation of STX3 in Exon 9 Causing Fatal Congenital Diarrheal Disease

Congenital diarrhea in a newborn infant: A case report

SNAREs and developmental disorders

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