u/HZLIZS

Not seeking medical advice, searching for similar cases. I’m hoping to connect with anyone who may have encountered a rare DOCK4 mutation, like the one that has presented in our family.

Our family recently identified the following variant through genetic testing:

Gene: DOCK4

Transcript: NM_001363540.2

Variant: c.2686C>T

Protein change: p.Arg896Ter

Genomic location (GRCh38): chr7:111844813 G>A

Zygosity: Heterozygous

Inheritance pattern observed: Dominant (maternal transmission)

This variant introduces a premature stop codon at amino acid position 896, truncating the DOCK4 protein.

DOCK4 is a large protein (~2000 amino acids), so this mutation removes more than half of the protein, including downstream functional regions such as the DHR2 catalytic domain, which is involved in Rac signaling and cytoskeletal regulation.

Because of this, the mutation likely represents a loss-of-function variant.

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So far the variant has been identified in multiple members:

• I carry the mutation (maternal carrier)

• My identical twins both tested positive

• My 13-year-old, who has an autism diagnosis, also tested positive, but he also was found to have a paternal AUTS2 mutation.

• Our 5-year-old is currently undergoing testing

This pattern suggests autosomal dominant inheritance with variable expression, possibly?

I have noticed a normal appearing facial structure for someone who is not familiar… but with specific features that are different. You wouldn’t notice anything in particular unless you knew. Flatter forehead, more straight sides, and specific eye set.

So far my 13 yr old son is 6’ tall, 160lbs, and wears a size 12 shoe. My twins are 2 years old and have remained in higher percentile for height. So now I’m curious because I’m only 5’7 so nothing wild with my height.

The other thing noticed is I have 2 fully formed extra ribs coming off of C7 and connecting fully in the front. No x-rays yet to confirm if my children with this mutation also have it.

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Why I’m posting

Our clinical team at Nationwide Children’s Hospital indicated that this exact variant appears to be extremely rare and never documented. The other DOCK4 mutations in medical journals have been denovo cases and not the same exact mutation. I have submitted the case to a rare-variant registry to help researchers potentially identify additional families.

However, because rare variants often go unrecognized, I’m trying to see whether:

• Other families may have DOCK4 mutations exactly like this one not found in medical journals?

• Anyone has observed familial inheritance patterns involving DOCK4?

• If anyone has this exact mutation and any health conditions?

DOCK4 sits in the chromosome 7q31 region, which has been discussed in literature related to neurodevelopmental conditions, but the clinical significance of individual variants still appears to be evolving.

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Looking to connect with

• Geneticists or researchers studying DOCK family proteins

• Families with this DOCK4 variant identified through genetic testing

• Clinicians who may have encountered similar cases

If anyone has encountered similar variants or is researching DOCK4, I’d really appreciate hearing from you.

#DOCK4

#RareVariant

#HumanGenetics

#GeneticsResearch

#RareDisease

#RareMutation

#UndiagnosedDisease

#Neurogenetics

#AutismResearch

#GeneMatcher

#VariantResearch

#PrecisionMedicine