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FAM177A1

Charlotte and Cooper are siblings with a rare disease caused by a variant on their FAM177A1 gene.  There are only a few other known cases in the world and very little is known about this gene. 

 

Our mission is to find more patients, expand research on this gene

and develop treatments. 

SYMPTOMS/PHENOTYPE

  • Loss of function of FAM177A1 gene

  • Intellectual disability

  • Autism

  • Large head size

  • Seizures

  • Sleep disturbance

  • Unusual gate or walking pattern

  • Congenital cataracts

  • Muscle tone issues

  • Upslanted palpebral fissues

  • Single transverse palmar crease (unilateral)

  • Clinodactyly of the 5th toe

  • 2-3 toe syndactyly​

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GENETIC FINDINGS

Charlotte and Cooper had exome sequencing done as part of a research study at the University of Washington and have also been followed by the Rare Genomics Institute.  There was initial hope that variants on the following genes might have caused their disease but there has been no further evidence to support this: LAMA5, NSD1and EZH2 genes.

In the spring of 2016, Charlotte and Cooper were accepted into the National Institute of Health’s Undiagnosed Diseases Network (NIH-UDN) program at Stanford University where extensive medical review and work-up was completed including whole genome sequencing.  Recently, upon repeat analysis of Charlotte and Cooper’s full genome sequence, a variant was found on both Charlotte and Cooper’s FAM177A1 gene that the UDN highly suspects caused their disease. The compound heterozygous deletions appear to have caused a loss of function (LOF) of the FAM177A1 gene in Charlotte and Cooper. These deletions have since been clinically validated.  There is very little known about this gene but functional studies are underway at the MOSC at Washington University in St. Louis using zebra fish.

Through a matching database, several other patients have been identified with similar genetic findings and overlapping clinical presentations.  There are also 4 siblings noted in a medical journal to have similar presentations and issues with this gene. The deletions identified in Charlotte and Cooper were detected in the genome sequencing data; however, homozygous nonsense and frameshift variants were identified in the other families via exome sequencing. So, it’s possible to identify additional families with LOF variants from exome data.

 

The coordinates of the deletions are:
– Chr14:35513595 – 35521629 (8kb) – encompasses exon 1
– Chr14:35546986 – 35556772 (9.7kb) – encompasses exons 4-5

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Health History

Do you know a child that is similar to our sweet rare zebras?  If so, get in touch with us. 

 

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