Genetics

The Biology of the Deletion: Genes and Inheritance

At a Glance

15q13.3 microdeletion syndrome is caused by a missing piece of chromosome 15 that typically includes the CHRNA7 and OTUD7A genes. About two-thirds of these deletions are inherited from a parent who may show no symptoms, while one-third occur spontaneously (de novo).

To understand 15q13.3 microdeletion syndrome, it helps to think of your child’s DNA as a massive library of instructions. Chromosomes are like the individual books in that library. Your child has a tiny piece of text missing from the middle of “Book 15” ^[1].

The Key Players: CHRNA7 and OTUD7A

While the missing segment is small, it usually contains several important genes. Two of the most critical are CHRNA7 and OTUD7A.

CHRNA7 (The Communicator): This gene provides the blueprint for a “receiver” on the surface of brain cells. This receiver helps cells pick up signals that control memory, learning, and attention ^[2]^[3]. When this gene is missing, the brain’s internal communication can become less efficient, which may lead to learning challenges or seizures ^[4]^[5].
OTUD7A (The Builder): This gene helps manage how brain cells (neurons) grow and connect to one another, specifically at the synapses (the tiny gaps where messages pass between cells) ^[6]. If this gene isn’t working properly, the “wiring” of the brain may develop differently, contributing to symptoms like autism or developmental delays ^[7]^[8].

How Did This Happen?

Genetic changes like this happen in one of two ways:

De Novo (A “New” Change): About 1/3 of cases are “de novo” ^[9]^[10]. This means the deletion occurred spontaneously in the egg or sperm, or very early in development. It is a random event, not caused by anything the parents did or didn’t do before or during pregnancy.
Inherited: About 2/3 of cases are inherited from a parent ^[9]. This is why doctors almost always recommend testing both biological parents.

The Mystery of “Reduced Penetrance”

You might wonder: If I passed this to my child, why am I healthy and they are struggling? This is explained by a concept called reduced (or incomplete) penetrance ^[11]^[12].

Think of the deletion like a “volume knob” that is turned down. In some people, the body’s other genes and the environment can “turn up the volume” to compensate, meaning they never show any symptoms and stay completely healthy ^[9]^[13]. In others, the same deletion leads to the symptoms we associate with the syndrome ^[14].

Testing parents isn’t about assigning “blame.” Instead, it helps doctors understand the family’s “genetic background.” If a parent has the deletion, it provides vital information about the chance of the condition appearing in future siblings and helps the parent understand their own health history, such as why they might have had mild learning struggles or a history of “staring spells” as a child ^[14]^[1].

Summary Table: Genetic Outlook

Feature	De Novo (1/3 of cases)	Inherited (2/3 of cases)
Origin	Spontaneous “glitch”	Passed from a parent
Parental Testing	Both parents will test negative	One parent will test positive
Risk for Siblings	Generally very low (<1%)	Up to 50% chance
Parent’s Health	Not applicable	Often asymptomatic (healthy) ^[9]

Every child’s genetic makeup is unique. While the deletion is the same, the way it interacts with the rest of your child’s DNA is what makes their journey unique ^[15]^[16].

Common questions in this guide

What genes are missing in 15q13.3 microdeletion syndrome?

The missing segment on chromosome 15 usually includes several important genes, with CHRNA7 and OTUD7A being the most critical. These genes play vital roles in how brain cells communicate, grow, and connect with one another.

Is 15q13.3 microdeletion inherited from a parent?

About two-thirds of cases are inherited from a parent, while one-third are 'de novo,' meaning they happen spontaneously. Doctors typically recommend genetic testing for both biological parents to understand how the deletion originated in the family.

Why would a parent with the 15q13.3 deletion be completely healthy?

A parent can carry the 15q13.3 deletion but remain healthy due to a concept called reduced penetrance. This means the body's other genes and environmental factors can compensate for the missing genetic instructions, preventing symptoms from developing.

What is the CHRNA7 gene responsible for?

The CHRNA7 gene provides instructions for a receptor on brain cells that helps process signals for memory, learning, and attention. When this gene is missing, it can cause the brain's internal communication to become less efficient, potentially leading to learning challenges or seizures.

Will my future children also have 15q13.3 microdeletion syndrome?

If neither parent has the deletion, the chance of future siblings having it is generally less than 1%. However, if one parent carries the deletion, there is up to a 50% chance of passing it to future children.

Curated prompts to bring to your next appointment.

1.Does my child's deletion include both the CHRNA7 and OTUD7A genes, or just one of them?
2.If one of us (the parents) tests positive for the deletion, what does that mean for our own health and for future children we might have?
3.Are there any 'secondary findings' on the genetic report we should be aware of?
4.Can you explain the difference between a heterozygous deletion and a homozygous deletion in the context of my child's specific results?

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References (16)

1
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PMID: 34601452
2
Functional Consequences of CHRNA7 Copy-Number Alterations in Induced Pluripotent Stem Cells and Neural Progenitor Cells.
Gillentine MA, Yin J, Bajic A, et al.
American journal of human genetics 2017; (101(6)):874-887 doi:10.1016/j.ajhg.2017.09.024.
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3
The Phenotypic Spectrum of 15q13.3 Region Duplications: Report of 5 Patients.
Budisteanu M, Papuc SM, Streata I, et al.
Genes 2021; (12(7)) doi:10.3390/genes12071025.
PMID: 34356041
4
Report of the first patient with a homozygous OTUD7A variant responsible for epileptic encephalopathy and related proteasome dysfunction.
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Clinical genetics 2020; (97(4)):567-575 doi:10.1111/cge.13709.
PMID: 31997314
5
Evaluation of multiple putative risk alleles within the 15q13.3 region for genetic generalized epilepsy.
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Epilepsy research 2015; (117()):70-3.
PMID: 26421493
6
Impaired OTUD7A-dependent Ankyrin regulation mediates neuronal dysfunction in mouse and human models of the 15q13.3 microdeletion syndrome.
Unda BK, Chalil L, Yoon S, et al.
Molecular psychiatry 2023; (28(4)):1747-1769 doi:10.1038/s41380-022-01937-5.
PMID: 36604605
7
Loss of function of OTUD7A in the schizophrenia- associated 15q13.3 deletion impairs synapse development and function in human neurons.
Kozlova A, Zhang S, Kotlar AV, et al.
American journal of human genetics 2022; (109(8)):1500-1519 doi:10.1016/j.ajhg.2022.07.001.
PMID: 35931052
8
The OTUD7A-Ankyrin pathway: a newly identified disease mechanism for the 15q13.3 microdeletion disorder.
Scheefhals N, Ciptasari U, van Hugte EJH, Nadif Kasri N
Molecular psychiatry 2023; (28(4)):1400-1401 doi:10.1038/s41380-023-01965-9.
PMID: 36670197
9
Genetic counseling of prenatally detected familial 15q13.2q13.3 microdeletion encompassing CHRNA7 and OTUD7A with asymptomatic carriers in the family.
Chen CP, Wu FT, Pan YT, et al.
Taiwanese journal of obstetrics & gynecology 2025; (64(2)):361-363 doi:10.1016/j.tjog.2024.12.015.
PMID: 40049827
10
FAN1, a DNA Repair Nuclease, as a Modifier of Repeat Expansion Disorders.
Deshmukh AL, Porro A, Mohiuddin M, et al.
Journal of Huntington's disease 2021; (10(1)):95-122 doi:10.3233/JHD-200448.
PMID: 33579867
11
The 15q13.3 deletion syndrome: Deficient α(7)-containing nicotinic acetylcholine receptor-mediated neurotransmission in the pathogenesis of neurodevelopmental disorders.
Deutsch SI, Burket JA, Benson AD, Urbano MR
Progress in neuro-psychopharmacology & biological psychiatry 2016; (64()):109-17.
PMID: 26257138
12
Case reports of two siblings with autism spectrum disorder and 15q13.3 deletions.
Furukawa S, Kushima I, Aleksic B, Ozaki N
Neuropsychopharmacology reports 2023; (43(3)):462-466 doi:10.1002/npr2.12340.
PMID: 37264739
13
Prenatal ultrasound phenotype of fetuses with recurrent 1q21.1 deletion and duplication syndrome.
Wang F, Peng H, Lou G, et al.
Frontiers in pediatrics 2024; (12()):1504122 doi:10.3389/fped.2024.1504122.
PMID: 39840309
14
The complex behavioral phenotype of 15q13.3 microdeletion syndrome.
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15
Network Effects of the 15q13.3 Microdeletion on the Transcriptome and Epigenome in Human-Induced Neurons.
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16
Interactive effects between hemizygous 15q13.3 microdeletion and peripubertal stress on adult behavioral functions.
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This page explains the genetics and inheritance of 15q13.3 microdeletion syndrome for educational purposes. Always consult a genetic counselor or pediatrician to discuss your family's specific genetic test results.

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