FAM111A Mutations Result in Hypoparathyroidism and Impaired Skeletal Development

Unger, Sheila; Górna, Maria W.; Béchec, Antony Le; Vale-Pereira, Sónia do; Bedeschi, Maria Francesca; Geiberger, Stefan; Grigelioniené, Giedré; Horemuzova, Eva; Lalatta, Faustina; Lausch, Ekkehart; Magnani, Cinzia; Nampoothiri, Sheela; Nishimura, Gen; Petrella, Duccio; Ringeling, Francisca Rojas; Utsunomiya, Akari; Zabel, Bernhard; Pradervand, Sylvain; Harshman, Keith; Campos‐Xavier, Belinda; Bonafé, Luisa; Superti‐Furga, Giulio; Stevenson, Brian J.; Superti‐Furga, Andrea

doi:10.1016/j.ajhg.2013.04.020

Cited by 124 publications

(177 citation statements)

References 19 publications

Supporting

Mentioning

167

Contrasting

Unclassified

Order By: Relevance

“…We identified a de novo heterozygous point mutation (c.1706G>A) in FAM111A causing a missense change (p.Arg569His). This is a known recurrent de novo variant causing the Kenny-Caffey syndrome, although she is the first patient with this diagnosis with documented normocalcemia [22, 23]. …”

Section: Resultsmentioning

confidence: 99%

Whole Exome Sequencing to Identify Genetic Causes of Short Stature

et al. 2014

View full text Add to dashboard Cite

Background/Aims: Short stature is a common reason for presentation to pediatric endocrinology clinics. However, for most patients, no cause for the short stature can be identified. As genetics plays a strong role in height, we sought to identify known and novel genetic causes of short stature. Methods: We recruited 14 children with severe short stature of unknown etiology. We conducted whole exome sequencing of the patients and their family members. We used an analysis pipeline to identify rare non-synonymous genetic variants that cause the short stature. Results: We identified a genetic cause of short stature in 5 of the 14 patients. This included cases of floating-harbor syndrome, Kenny-Caffey syndrome, the progeroid form of Ehlers-Danlos syndrome, as well as 2 cases of the 3-M syndrome. For the remaining patients, we have generated lists of candidate variants. Conclusions: Whole exome sequencing can help identify genetic causes of short stature in the context of defined genetic syndromes, but may be less effective in identifying novel genetic causes of short stature in individual families. Utilized in the clinic, whole exome sequencing can provide clinically relevant diagnoses for these patients. Rare syndromic causes of short stature may be underrecognized and underdiagnosed in pediatric endocrinology clinics.

show abstract

Section: Resultsmentioning

confidence: 99%

Whole Exome Sequencing to Identify Genetic Causes of Short Stature

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Because FAM111A exhibits cell cycledependent expression (45), and as we have shown here is induced by IFN, IRF2 might not be needed for induction under some conditions. Mutations of FAM111A cause Kenny-Caffey syndrome (46,47), hypoparathyriodism, and impaired skeletal development (48). Interestingly, FAM111A is a host restriction factor for an SV40 mutant (34).…”

Section: Discussionmentioning

confidence: 99%

Triad of human cellular proteins, IRF2, FAM111A, and RFC3, restrict replication of orthopoxvirus SPI-1 host-range mutants

Panda

Fernández

Lal

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Viruses and their hosts can reach balanced states of evolution ensuring mutual survival, which makes it difficult to appreciate the underlying dynamics. To uncover hidden interactions, virus mutants that have lost defense genes may be used. Deletion of the gene that encodes serine protease inhibitor 1 (SPI-1) of rabbitpox virus and vaccinia virus, two closely related orthopoxviruses, prevents their efficient replication in human cells, whereas certain other mammalian cells remain fully permissive. Our highthroughput genome-wide siRNA screen identified host factors that prevent reproduction and spread of the mutant viruses in human cells. More than 20,000 genes were interrogated with individual siRNAs and those that prominently increased replication of the SPI-1 deletion mutant were subjected to a secondary screen. The top hits based on the combined data-replication factor C3 (RFC3), FAM111A, and interferon regulatory factor 2 (IRF2)-were confirmed by custom assays. The siRNAs to RFC1, RFC2, RFC4, and RFC5 mRNAs also enhanced spread of the mutant virus, strengthening the biological significance of the RFC complex as a host restriction factor for poxviruses. Whereas association with proliferating cell nuclear antigen and participation in processive genome replication are common features of FAM111A and RFC, IRF2 is a transcriptional regulator. Microarray analysis, quantitative RT-PCR, and immunoblotting revealed that IRF2 regulated the basal level expression of FAM111A, suggesting that the enhancing effect of depleting IRF2 on replication of the SPI-1 mutant was indirect. Thus, the viral SPI-1 protein and the host IRF2, FAM111A, and RFC complex likely form an interaction network that influences the ability of poxviruses to replicate in human cells.poxviruses | host range | DNA replication factors | interferon regulatory factor | RNAi screen

show abstract

“…The aforementioned brain-expressed genes associated with RFSs also show high expression in the reproductive organs (Uhlen et al 2010). In addition, FAM11A gene expression is high in bone marrow, nervous system, and endocrine glands (Unger et al 2013). Finally, there seems to be a dominance of neurological disorders, as opposed to cancer, associated with RFSs for unknown reasons.…”

Section: Classification Of “Common” Vs “Rare” Fragile Sitesmentioning

confidence: 99%

Fragility Extraordinaire: Unsolved Mysteries of Chromosome Fragile Sites

Feng

Chakraborty

2017

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Chromosome fragile sites are a fascinating cytogenetic phenomenon now widely implicated in a slew of human diseases ranging from neurological disorders to cancer. Yet, the paths leading to these revelations were far from direct, and the number of fragile sites that have been molecularly cloned with known disease-associated genes remains modest. Moreover, as more fragile sites were being discovered, research interests in some of the earliest discovered fragile sites ebbed away, leaving a number of unsolved mysteries in chromosome biology. In this review we attempt to recount some of the early discoveries of fragile sites and highlight those phenomena that have eluded intense scrutiny but remain extremely relevant in our understanding of the mechanisms of chromosome fragility. We then survey the literature for disease association for a comprehensive list of fragile sites. We also review recent studies addressing the underlying cause of chromosome fragility while highlighting some ongoing debates. We report an observed enrichment for R-loop forming sequences in fragile site-associated genes than genomic average. Finally, we will leave the reader with some lingering questions to provoke discussion and inspire further scientific inquiries.

show abstract

FAM111A Mutations Result in Hypoparathyroidism and Impaired Skeletal Development

Cited by 124 publications

References 19 publications

Whole Exome Sequencing to Identify Genetic Causes of Short Stature

Whole Exome Sequencing to Identify Genetic Causes of Short Stature

Triad of human cellular proteins, IRF2, FAM111A, and RFC3, restrict replication of orthopoxvirus SPI-1 host-range mutants

Fragility Extraordinaire: Unsolved Mysteries of Chromosome Fragile Sites

Contact Info

Product

Resources

About