A complex Xp11.22 deletion in a patient with syndromic autism: Exploration of FAM120C as a positional candidate gene for autism

Abstract

We present a male patient with sporadic Aarskog syndrome, cleft palate, mild intellectual disability, and autism spectrum disorder (ASD). A submicroscopic discontiguous deletion was detected on chromosome Xp11.2 encompassing FGD1, FAM120C, and PHF8. That the deletion encompassed FGD1 (exons 2-8) explains the Aarskog features while the deletion of PHF8 most likely explains the cleft palate and mild intellectual disability. We identify FAM120C as a novel X-linked candidate gene for autism for two reasons: first, a larger deletion encompassing FAM120C segregates with autism in a previously reported family and second, there is recent evidence that FAM120C interacts with CYFIP1, part of the FMRP (Fragile X Mental Retardation Protein) network. In the current study, resequencing of FAM120C in 87 Belgian male patients with autism spectrum disorder identified no novel mutations. Expression of Fam120c in mouse tissues showed enriched expression in pituitary, cerebellum, cortex, and pancreatic islets of Langerhans. Additionally, we found a cortical expression pattern of Fam120c similar to that of Fmr1. In conclusion, FAM120C is a novel candidate gene for autism spectrum disorder based on genetic evidence and the brain expression pattern. Thereby we highlight a role for FMRP network genes in ASD.

Mapping cell structure across scales by fusing protein images and interactions

“…4o). The close associations of FAM120C, a candidate disease protein in autism spectrum disorder 43 , with proteins involved in regulation of chromatin suggests a novel function for this protein, consistent with the previous identification of other chromatin factors in autism 44 .…”

Hippocampal Transcriptomic and Proteomic Alterations in the BTBR Mouse Model of Autism Spectrum Disorder

“…From the transcript analysis, we identified the involvement of neurexin 1 (Yangngam et al, 2014 ) and Wolframin syndrome 1 (Wfs1; Chakrabarti et al, 2009 ). From the protein analysis, we again identified Wfs1 as a strong autism-related link, Fam120c (De Wolf et al, 2014 ), and Bassoon (Bsn; Yoshida et al, 2011 ). Therefore, the only factor that was strongly implicated in both the transcriptomic and proteomic hippocampal BTBR profiles was Wfs1.…”

Xp11.22 deletions encompassing CENPVL1, CENPVL2, MAGED1 and GSPT2 as a cause of syndromic X-linked intellectual disability

“…Armeanet et al identified a male with developmental delay and intellectual disability who carried an Xp11.22 deletion involving SHROOM4 and intellectual disability and autism has been described by Qiao et al and De Wolf et al in males carrying Xp11.22 deletions that included PHF8 and FAM120C [1,6,9]. Mutations of SHROOM4 have been reported to cause Stocco dos Santos X-linked mental retardation syndrome [OMIM #300579] and mutations of PHF8 cause mental retardation syndrome, X-linked, Siderius type [OMIM # 300560] [24–28].…”

“…Mutations of SHROOM4 have been reported to cause Stocco dos Santos X-linked mental retardation syndrome [OMIM #300579] and mutations of PHF8 cause mental retardation syndrome, X-linked, Siderius type [OMIM # 300560] [24–28]. Although mutations of FAM120C have not been associated with a particular human phenotype, this gene has been proposed as a positional candidate gene for autism based on its expression pattern in the brain and FAM120C’s interaction with CYFIP1, an important binding partner of the fragile X mental retardation protein (FMRP) [6,29]. …”