₦airaland Forum

Yep! You read that well and interestingly, most healthcare providers around the worldbdo not know this science.
The most likely explanation involves a mutation or undetected variant affecting the hemoglobin gene. Here are possibilities:

1️. “AA” parent actually has a silent or rare sickle mutation (e.g. β⁰-thalassemia, HbC, or HbD)
What happens: Some people test as AA on standard tests because they have a rare variant of the beta-globin gene that isn’t picked up by routine electrophoresis or sickle solubility tests.
If that parent actually carries a rare abnormal hemoglobin (like HbC, HbD Punjab, HbE, or β-thalassemia mutation), then pairing with AS could result in compound heterozygosity (e.g., SC, Sβ⁰-thalassemia).

Some of these combinations can behave clinically like SS (sickle cell disease).

🩺 How to test: Advanced testing like DNA sequencing of the HBB gene, or HPLC (High-Performance Liquid Chromatography) instead of standard electrophoresis.

2️⃣ De novo mutation (new S mutation arising during gamete formation)
What happens: A mutation spontaneously occurs in the sperm or egg, converting an A allele to an S allele. In simple terms your so called 'A' trait/gene reconstitutes itself into an 'S' gene.

This is very rare in sickle cell disease because the S mutation (Glu6Val) is well established in populations, but not impossible.

Estimated de novo mutation rate for the HBB gene is low, but if it happened in a germline mosaicism (parent has S mutation in some germ cells but not in blood), they can pass it on without showing AS in tests.

3️⃣ Laboratory testing error / Misclassification
This has happened in some regions where only solubility tests or basic electrophoresis were used.

If the "AA" status was determined long ago or outside of a specialized center, consider repeat testing with HPLC or molecular methods.

❓ Usually, this sort of trait as explained in 1 above can run in a family leading to lots of SID (sudden infant death) or lots of observed fatalities despite 'correct genotype match'

This obviously suggests an inherited silent or rare variant running in the family.
If multiple AA x AS couples are having SS children:
✅ More likely explanation: a family-wide rare hemoglobin variant or HBB mutation masquerading as "AA" in standard testing.

Think of it as a hidden carrier state.

🧪 What you should do to get better clarification.

Ask for:
✅ HBB gene sequencing (to check for all beta-globin mutations).
✅ HPLC or Capillary Electrophoresis (to detect rare hemoglobin variants).
✅ Parental genotyping (especially the so-called “AA” parent).

Seun

ChristCee:
Yep! You read that well and interestingly, most healthcare providers around the worldbdo not know this science.
The most likely explanation involves a mutation or undetected variant affecting the hemoglobin gene. Here are possibilities:

1️. “AA” parent actually has a silent or rare sickle mutation (e.g. β⁰-thalassemia, HbC, or HbD)
What happens: Some people test as AA on standard tests because they have a rare variant of the beta-globin gene that isn’t picked up by routine electrophoresis or sickle solubility tests.
If that parent actually carries a rare abnormal hemoglobin (like HbC, HbD Punjab, HbE, or β-thalassemia mutation), then pairing with AS could result in compound heterozygosity (e.g., SC, Sβ⁰-thalassemia).

Some of these combinations can behave clinically like SS (sickle cell disease).

🩺 How to test: Advanced testing like DNA sequencing of the HBB gene, or HPLC (High-Performance Liquid Chromatography) instead of standard electrophoresis.

2️⃣ De novo mutation (new S mutation arising during gamete formation)
What happens: A mutation spontaneously occurs in the sperm or egg, converting an A allele to an S allele. In simple terms your so called 'A' trait/gene reconstitutes itself into an 'S' gene.

This is very rare in sickle cell disease because the S mutation (Glu6Val) is well established in populations, but not impossible.

Estimated de novo mutation rate for the HBB gene is low, but if it happened in a germline mosaicism (parent has S mutation in some germ cells but not in blood), they can pass it on without showing AS in tests.

3️⃣ Laboratory testing error / Misclassification
This has happened in some regions where only solubility tests or basic electrophoresis were used.

If the "AA" status was determined long ago or outside of a specialized center, consider repeat testing with HPLC or molecular methods.

❓ Usually, this sort of trait as explained in 1 above can run in a family leading to lots of SID (sudden infant death) or lots of observed fatalities despite 'correct genotype match'

This obviously suggests an inherited silent or rare variant running in the family.
If multiple AA x AS couples are having SS children:
✅ More likely explanation: a family-wide rare hemoglobin variant or HBB mutation masquerading as "AA" in standard testing.

Think of it as a hidden carrier state.

🧪 What you should do to get better clarification.

Ask for:
✅ HBB gene sequencing (to check for all beta-globin mutations).
✅ HPLC or Capillary Electrophoresis (to detect rare hemoglobin variants).
✅ Parental genotyping (especially the so-called “AA” parent).

Seun

This is serious.

Neris:
This is serious.

It really is. Sadly biology is no longer a compulsory subject for high school students in most states.

You are 100% right but me and you knows it is copy and paste

ChristCee:
Yep! You read that well and interestingly, most healthcare providers around the worldbdo not know this science.
The most likely explanation involves a mutation or undetected variant affecting the hemoglobin gene. Here are possibilities:

1️. “AA” parent actually has a silent or rare sickle mutation (e.g. β⁰-thalassemia, HbC, or HbD)
What happens: Some people test as AA on standard tests because they have a rare variant of the beta-globin gene that isn’t picked up by routine electrophoresis or sickle solubility tests.
If that parent actually carries a rare abnormal hemoglobin (like HbC, HbD Punjab, HbE, or β-thalassemia mutation), then pairing with AS could result in compound heterozygosity (e.g., SC, Sβ⁰-thalassemia).

Some of these combinations can behave clinically like SS (sickle cell disease).

🩺 How to test: Advanced testing like DNA sequencing of the HBB gene, or HPLC (High-Performance Liquid Chromatography) instead of standard electrophoresis.

2️⃣ De novo mutation (new S mutation arising during gamete formation)
What happens: A mutation spontaneously occurs in the sperm or egg, converting an A allele to an S allele. In simple terms your so called 'A' trait/gene reconstitutes itself into an 'S' gene.

This is very rare in sickle cell disease because the S mutation (Glu6Val) is well established in populations, but not impossible.

Estimated de novo mutation rate for the HBB gene is low, but if it happened in a germline mosaicism (parent has S mutation in some germ cells but not in blood), they can pass it on without showing AS in tests.

3️⃣ Laboratory testing error / Misclassification
This has happened in some regions where only solubility tests or basic electrophoresis were used.

If the "AA" status was determined long ago or outside of a specialized center, consider repeat testing with HPLC or molecular methods.

❓ Usually, this sort of trait as explained in 1 above can run in a family leading to lots of SID (sudden infant death) or lots of observed fatalities despite 'correct genotype match'

This obviously suggests an inherited silent or rare variant running in the family.
If multiple AA x AS couples are having SS children:
✅ More likely explanation: a family-wide rare hemoglobin variant or HBB mutation masquerading as "AA" in standard testing.

Think of it as a hidden carrier state.

🧪 What you should do to get better clarification.

Ask for:
✅ HBB gene sequencing (to check for all beta-globin mutations).
✅ HPLC or Capillary Electrophoresis (to detect rare hemoglobin variants).
✅ Parental genotyping (especially the so-called “AA” parent).

Seun

Redoil:
You are 100% right but me and you knows it is copy and paste

Medical student practicing and training in Russia.
You should see my research on Tinnitus. 🙌