Elena & Sam
Sample POC-1 · Report 2026-08-21
Clinical summary · POC-1
A likely single-gene explanation for this loss: two CPLANE1 variants, one from each of you.
First-trimester loss · ~9 weeks
In plain language
The clinic's chromosome test was normal (46,XY), and checking it against both of your genomes confirmed the sample came from the pregnancy itself.
Each of you carries one pathogenic CPLANE1 variant; this pregnancy inherited both.
Together they are a likely explanation for this loss — not its proven cause.
The finding
Linked to Joubert syndrome
CPLANE1 helps build cilia — the tiny antennae cells use to steer how a body is laid out in the first weeks. Two pathogenic copies cause Joubert syndrome, a rare condition affecting how the brain forms. Autosomal recessive — carriers with one copy are healthy.
Elena
egg source
Carrierc.493del (p.Ile165fs)
Known to be harmful (pathogenic)
Sam
sperm source
Carrierc.6354dup (p.Ile2119fs)
Known to be harmful (pathogenic / likely pathogenic)
This pregnancy
POC-1
Both copiesBoth variants, one from each
Compound heterozygous · Confidence: High
What this result means for me
Christina's counselor note
Reviewed by Christina, Genetic Counselor
What to know
- Nothing either of you did caused this — a carrier copy is silent, and common.
- In the largest study of its kind, about 1 in 4 couples with unexplained, recurrent loss — two or more, all chromosomally normal — had a possible single-gene cause, usually inherited from one or both parents (30 of 118 families; Aminbeidokhti et al., 2025 preprint).
- In that same study, 95% of the losses had shown nothing on ultrasound — a normal scan was never evidence against a genetic cause.
What it doesn't mean
- Carriers are healthy — one copy doesn't affect your health, or a child's.
- A likely explanation is not a proven cause — not a diagnosis of any person or pregnancy — and this kind of re-analysis is an emerging approach, not yet routine practice.
- It doesn't evaluate the other causes of loss — uterine, hormonal, immune, or clotting.
When you're ready
- Book your included counseling session — we'll go through this finding together, question by question.
How CPLANE1 is inherited
Many couples with a finding like this go on to have healthy pregnancies.
What you can do next
A positive result is a starting point, not a verdict. These are the options most couples discuss after a finding like this.
Talk it through with your genetic counselor
A session with Reticular's genetic counselor is included — no referral needed. We'll go through what the CPLANE1 finding means for you, so you take a clear picture into your next clinic visit.
Why didn’t carrier screening catch this?
Carrier screening asks a different question: whether the two of you carry a variant that could affect a future child’s health. It reports carrier status in the parents; it does not read what a pregnancy inherited, and its panels are built around conditions that appear after birth — so genes tied to pregnancy loss are largely absent. CPLANE1 is not on the gene list ACMG recommends for carrier screening, and no major professional guideline includes carrier screening in the evaluation of pregnancy loss. A carrier screen was not the wrong test; it was a different one.
What the panel screened
750+ genes
grouped by biological mechanism
Both of your genomes were read across every group below and compared with the pregnancy's chromosome-test data to work out which copies it inherited. Each group shows its full gene list; only a change worth reporting is called out above.
Genes that help the egg mature and divide
18 genes · full list
These genes help an egg finish maturing and line up its chromosomes to divide. A fault can leave eggs unable to mature, or embryos stalling in the first few days — before a pregnancy can take hold.
Gene list sources: ESHRE FeRGI Database · Curated published literature
Genes for fertilization
10 genes · full list
These genes handle fertilization — the egg's outer coat (the zona pellucida) and the signal sperm use to switch the egg on. A fault can cause fertilization to fail even when the egg and sperm look normal.
Gene list sources: ESHRE FeRGI Database · Curated published literature
Genes that run the embryo's first days
12 genes · full list
The egg stores a “starter kit” of genes that run the embryo's first divisions. A fault makes embryos stop growing at the same early stage, cycle after cycle — a signal that points to egg biology, not anything either of you did.
Gene list sources: ESHRE FeRGI Database · Curated published literature
Genes tied to molar pregnancy
5 genes · full list
These genes set the maternal “imprint” (a chemical tag on the egg's genes) that an embryo needs. A fault can cause molar pregnancies — abnormal tissue growth instead of a healthy pregnancy — and repeat losses that trace to egg biology, with any partner.
Gene list source: ESHRE FeRGI Database
Genes for ovarian reserve & egg supply
43 genes · full list
These genes maintain the egg supply and keep the ovaries working on schedule. A fault can mean fewer eggs, a poor response to stimulation, or ovarian insufficiency earlier than expected — knowledge that changes how quickly to act.
Gene list source: ESHRE FeRGI Database
Genes for the hormones that drive ovulation
26 genes · full list
Hormone-signaling genes — the brain-to-ovary axis that triggers egg maturation and release, plus genes tied to PCOS. A fault can mean absent or irregular ovulation, which is often very treatable once the cause is known.
Gene list source: ESHRE FeRGI Database
Genes a pregnancy needs to keep growing
182 genes · full list
Genes an embryo or fetus needs to keep developing through pregnancy, from the published Human Intolerome. If both partners carry a fault in the same gene, about 1 in 4 pregnancies can inherit both — a cause of loss that standard chromosome testing can't see. This report's CPLANE1 finding belongs to this group — it comes from the same database's emerging-evidence tier, so it's screened but not listed below.
Gene list source: RPLdb Human Intolerome
Genes a newborn needs to thrive
377 genes · full list
Severe recessive conditions that appear after birth rather than during pregnancy. If both partners carry the same gene, each child has a 1-in-4 chance, so these are reported for family planning — the way classic carrier screening works — not as a cause of pregnancy loss.
Gene list source: RPLdb Human Intolerome
Blood-clotting & pregnancy-support genes
12 genes · full list
Clotting and pregnancy-support genes — like Factor V Leiden (F5) — that can raise the risk of later loss. Their link to early loss is weaker and depends on the whole clinical picture.
Gene list sources: ESHRE FeRGI Database · Curated published literature
Genes for sperm
34 genes · full list
Genes for making and shaping sperm. A fault can lower the count, slow movement, or change shape — and helps show whether a lab step that injects a single sperm into an egg (called ICSI), or another step, would help.
Gene list source: Curated published literature
Gene lists follow published evidence tiers: the pregnancy and newborn groups hold the “Known”-evidence genes of the 934-entry Human Intolerome, split by the database's own record of when a fault is lethal (emerging and candidate research genes are screened but not listed individually), and the infertility groups list every ESHRE FeRGI gene with moderate-or-stronger gene–disease evidence (score 9–18 of 18). Each gene is listed once in its best-fitting group — except MSH4, STAG3, and SYCE1, which appear under both ovarian reserve and sperm because they act in meiosis in both sexes. The 750+ total is cross-referenced against other laboratories' infertility panels.