Identification of Two CRB1 and AHI1 Pathogenetic Variants in an Iranian Family with Two Syndromic and Non-Syndromic Inherited Retinal Disorders

Fahimeh Beigi; Masoud Reza Manaviat; Nasrin Ghasemi

doi:doi:10.11648/j.ijmri.20260201.13

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Identification of Two CRB1 and AHI1 Pathogenetic Variants in an Iranian Family with Two Syndromic and Non-Syndromic Inherited Retinal Disorders

Fahimeh Beigi

, Masoud Reza Manaviat, Nasrin Ghasemi^*

Published in International Journal of Medical Research and Innovation (Volume 2, Issue 1)

Received: 15 October 2025 Accepted: 8 December 2025 Published: 29 December 2025

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Abstract

Background: Leber congenital amaurosis (LCA) is one of the most common inherited retinal disorders characterized by rod-cone dystrophy nystagmus, strabismus, with decreased vision after birth, photophobia, cataracts and keratoconus. In the study, we found different genotypes in patients with two different non-syndromic and syndromic patterns in an Iranian family with autosomal recessive retinitis pigmentosa (arRP). Materials and methods: The proband’s variant were detected by Next Generation Sequencing (NGS) using True Sight One Clinical Exome (TSO) panel of 234 genes related to Inherited retinal dystrophies. The pathogenicity of the variants was determined based on their allele frequency in the Genome aggregation database (gnomAD), In silico prediction tools for new missense and splicing variants, following that it performed cosegregation data in the family. The variants were confirmed by Sanger sequencing using specific primers. Results: Molecular study of NGS and following sanger sequencing showed two variants in different CRB1 and AHI1 genes in the patients of family. In the study in proband (VI:2) revealed a homozygous frameshift variant in the exon 6 of the CRB1 gene (NM_201253.2; c.1576C>T; p. (Arg526*)) and in other member of the family a homozygous missense variant in the exon 15 of the AHI1 gene. Patients affected to LCA and a patient affected to Joubert syndrome (JBTS) presented different clinical features. Conclusions: In the present study. NGS is considered as the most new and powerful sequencing technique to detect causal variants in different genes. In the family identified two different molecular genetic characteristics of patients with (LCA) and mild JBTS which is involved retinal degeneration which are known to cause severe inherited retinal dystrophies.

Published in	International Journal of Medical Research and Innovation (Volume 2, Issue 1)
DOI	10.11648/j.ijmri.20260201.13
Page(s)	17-22
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2025. Published by Science Publishing Group

Keywords

Leber Congenital Amaurosis (LCA), Autosomal Recessive Retinitis Pigmentosa (arRP), Next Generation Sequencing (NGS), CRB1, AHI1, Joubert Syndrome (JS)

References

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[24]	Beryozkin, A., Zelinger, L., Bandah-Rozenfeld, D., Harel, A., Strom, T. A., Merin, S., et al. Mutations in CRB1 are a relatively common cause of autosomal recessive early-onset retinal degeneration in the Israeli and Palestinian populations. Investigative Ophthalmology & Visual Science, 2013, 54(3), 2068–2075. https://doi.org/10.1167/iovs.12-11419
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APA Style

Beigi, F., Manaviat, M. R., Ghasemi, N. (2025). Identification of Two CRB1 and AHI1 Pathogenetic Variants in an Iranian Family with Two Syndromic and Non-Syndromic Inherited Retinal Disorders. International Journal of Medical Research and Innovation, 2(1), 17-22. https://doi.org/10.11648/j.ijmri.20260201.13

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ACS Style

Beigi, F.; Manaviat, M. R.; Ghasemi, N. Identification of Two CRB1 and AHI1 Pathogenetic Variants in an Iranian Family with Two Syndromic and Non-Syndromic Inherited Retinal Disorders. Int. J. Med. Res. Innovation 2025, 2(1), 17-22. doi: 10.11648/j.ijmri.20260201.13

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AMA Style

Beigi F, Manaviat MR, Ghasemi N. Identification of Two CRB1 and AHI1 Pathogenetic Variants in an Iranian Family with Two Syndromic and Non-Syndromic Inherited Retinal Disorders. Int J Med Res Innovation. 2025;2(1):17-22. doi: 10.11648/j.ijmri.20260201.13

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@article{10.11648/j.ijmri.20260201.13,
  author = {Fahimeh Beigi and Masoud Reza Manaviat and Nasrin Ghasemi},
  title = {Identification of Two CRB1 and AHI1 Pathogenetic Variants in an Iranian Family with Two Syndromic and Non-Syndromic Inherited Retinal Disorders},
  journal = {International Journal of Medical Research and Innovation},
  volume = {2},
  number = {1},
  pages = {17-22},
  doi = {10.11648/j.ijmri.20260201.13},
  url = {https://doi.org/10.11648/j.ijmri.20260201.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijmri.20260201.13},
  abstract = {Background: Leber congenital amaurosis (LCA) is one of the most common inherited retinal disorders characterized by rod-cone dystrophy nystagmus, strabismus, with decreased vision after birth, photophobia, cataracts and keratoconus. In the study, we found different genotypes in patients with two different non-syndromic and syndromic patterns in an Iranian family with autosomal recessive retinitis pigmentosa (arRP). Materials and methods: The proband’s variant were detected by Next Generation Sequencing (NGS) using True Sight One Clinical Exome (TSO) panel of 234 genes related to Inherited retinal dystrophies. The pathogenicity of the variants was determined based on their allele frequency in the Genome aggregation database (gnomAD), In silico prediction tools for new missense and splicing variants, following that it performed cosegregation data in the family. The variants were confirmed by Sanger sequencing using specific primers. Results: Molecular study of NGS and following sanger sequencing showed two variants in different CRB1 and AHI1 genes in the patients of family. In the study in proband (VI:2) revealed a homozygous frameshift variant in the exon 6 of the CRB1 gene (NM_201253.2; c.1576C>T; p. (Arg526*)) and in other member of the family a homozygous missense variant in the exon 15 of the AHI1 gene. Patients affected to LCA and a patient affected to Joubert syndrome (JBTS) presented different clinical features. Conclusions: In the present study. NGS is considered as the most new and powerful sequencing technique to detect causal variants in different genes. In the family identified two different molecular genetic characteristics of patients with (LCA) and mild JBTS which is involved retinal degeneration which are known to cause severe inherited retinal dystrophies.},
 year = {2025}
}

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TY  - JOUR
T1  - Identification of Two CRB1 and AHI1 Pathogenetic Variants in an Iranian Family with Two Syndromic and Non-Syndromic Inherited Retinal Disorders
AU  - Fahimeh Beigi
AU  - Masoud Reza Manaviat
AU  - Nasrin Ghasemi
Y1  - 2025/12/29
PY  - 2025
N1  - https://doi.org/10.11648/j.ijmri.20260201.13
DO  - 10.11648/j.ijmri.20260201.13
T2  - International Journal of Medical Research and Innovation
JF  - International Journal of Medical Research and Innovation
JO  - International Journal of Medical Research and Innovation
SP  - 17
EP  - 22
PB  - Science Publishing Group
UR  - https://doi.org/10.11648/j.ijmri.20260201.13
AB  - Background: Leber congenital amaurosis (LCA) is one of the most common inherited retinal disorders characterized by rod-cone dystrophy nystagmus, strabismus, with decreased vision after birth, photophobia, cataracts and keratoconus. In the study, we found different genotypes in patients with two different non-syndromic and syndromic patterns in an Iranian family with autosomal recessive retinitis pigmentosa (arRP). Materials and methods: The proband’s variant were detected by Next Generation Sequencing (NGS) using True Sight One Clinical Exome (TSO) panel of 234 genes related to Inherited retinal dystrophies. The pathogenicity of the variants was determined based on their allele frequency in the Genome aggregation database (gnomAD), In silico prediction tools for new missense and splicing variants, following that it performed cosegregation data in the family. The variants were confirmed by Sanger sequencing using specific primers. Results: Molecular study of NGS and following sanger sequencing showed two variants in different CRB1 and AHI1 genes in the patients of family. In the study in proband (VI:2) revealed a homozygous frameshift variant in the exon 6 of the CRB1 gene (NM_201253.2; c.1576C>T; p. (Arg526*)) and in other member of the family a homozygous missense variant in the exon 15 of the AHI1 gene. Patients affected to LCA and a patient affected to Joubert syndrome (JBTS) presented different clinical features. Conclusions: In the present study. NGS is considered as the most new and powerful sequencing technique to detect causal variants in different genes. In the family identified two different molecular genetic characteristics of patients with (LCA) and mild JBTS which is involved retinal degeneration which are known to cause severe inherited retinal dystrophies.
VL  - 2
IS  - 1
ER  -

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Author Information

Fahimeh Beigi

Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran;Department of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Science, Isfahan, Iran

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http://orcid.org/0000-0001-7666-4290
Masoud Reza Manaviat

Department of Ophthalmology, Shahid Sadoughi University of Medical Science, Yazd, Iran
Nasrin Ghasemi

Abortion Research and Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

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APA Style

Beigi, F., Manaviat, M. R., Ghasemi, N. (2025). Identification of Two CRB1 and AHI1 Pathogenetic Variants in an Iranian Family with Two Syndromic and Non-Syndromic Inherited Retinal Disorders. International Journal of Medical Research and Innovation, 2(1), 17-22. https://doi.org/10.11648/j.ijmri.20260201.13

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ACS Style

Beigi, F.; Manaviat, M. R.; Ghasemi, N. Identification of Two CRB1 and AHI1 Pathogenetic Variants in an Iranian Family with Two Syndromic and Non-Syndromic Inherited Retinal Disorders. Int. J. Med. Res. Innovation 2025, 2(1), 17-22. doi: 10.11648/j.ijmri.20260201.13

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AMA Style

Beigi F, Manaviat MR, Ghasemi N. Identification of Two CRB1 and AHI1 Pathogenetic Variants in an Iranian Family with Two Syndromic and Non-Syndromic Inherited Retinal Disorders. Int J Med Res Innovation. 2025;2(1):17-22. doi: 10.11648/j.ijmri.20260201.13

Copy | Download

@article{10.11648/j.ijmri.20260201.13,
  author = {Fahimeh Beigi and Masoud Reza Manaviat and Nasrin Ghasemi},
  title = {Identification of Two CRB1 and AHI1 Pathogenetic Variants in an Iranian Family with Two Syndromic and Non-Syndromic Inherited Retinal Disorders},
  journal = {International Journal of Medical Research and Innovation},
  volume = {2},
  number = {1},
  pages = {17-22},
  doi = {10.11648/j.ijmri.20260201.13},
  url = {https://doi.org/10.11648/j.ijmri.20260201.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijmri.20260201.13},
  abstract = {Background: Leber congenital amaurosis (LCA) is one of the most common inherited retinal disorders characterized by rod-cone dystrophy nystagmus, strabismus, with decreased vision after birth, photophobia, cataracts and keratoconus. In the study, we found different genotypes in patients with two different non-syndromic and syndromic patterns in an Iranian family with autosomal recessive retinitis pigmentosa (arRP). Materials and methods: The proband’s variant were detected by Next Generation Sequencing (NGS) using True Sight One Clinical Exome (TSO) panel of 234 genes related to Inherited retinal dystrophies. The pathogenicity of the variants was determined based on their allele frequency in the Genome aggregation database (gnomAD), In silico prediction tools for new missense and splicing variants, following that it performed cosegregation data in the family. The variants were confirmed by Sanger sequencing using specific primers. Results: Molecular study of NGS and following sanger sequencing showed two variants in different CRB1 and AHI1 genes in the patients of family. In the study in proband (VI:2) revealed a homozygous frameshift variant in the exon 6 of the CRB1 gene (NM_201253.2; c.1576C>T; p. (Arg526*)) and in other member of the family a homozygous missense variant in the exon 15 of the AHI1 gene. Patients affected to LCA and a patient affected to Joubert syndrome (JBTS) presented different clinical features. Conclusions: In the present study. NGS is considered as the most new and powerful sequencing technique to detect causal variants in different genes. In the family identified two different molecular genetic characteristics of patients with (LCA) and mild JBTS which is involved retinal degeneration which are known to cause severe inherited retinal dystrophies.},
 year = {2025}
}

Copy | Download

TY  - JOUR
T1  - Identification of Two CRB1 and AHI1 Pathogenetic Variants in an Iranian Family with Two Syndromic and Non-Syndromic Inherited Retinal Disorders
AU  - Fahimeh Beigi
AU  - Masoud Reza Manaviat
AU  - Nasrin Ghasemi
Y1  - 2025/12/29
PY  - 2025
N1  - https://doi.org/10.11648/j.ijmri.20260201.13
DO  - 10.11648/j.ijmri.20260201.13
T2  - International Journal of Medical Research and Innovation
JF  - International Journal of Medical Research and Innovation
JO  - International Journal of Medical Research and Innovation
SP  - 17
EP  - 22
PB  - Science Publishing Group
UR  - https://doi.org/10.11648/j.ijmri.20260201.13
AB  - Background: Leber congenital amaurosis (LCA) is one of the most common inherited retinal disorders characterized by rod-cone dystrophy nystagmus, strabismus, with decreased vision after birth, photophobia, cataracts and keratoconus. In the study, we found different genotypes in patients with two different non-syndromic and syndromic patterns in an Iranian family with autosomal recessive retinitis pigmentosa (arRP). Materials and methods: The proband’s variant were detected by Next Generation Sequencing (NGS) using True Sight One Clinical Exome (TSO) panel of 234 genes related to Inherited retinal dystrophies. The pathogenicity of the variants was determined based on their allele frequency in the Genome aggregation database (gnomAD), In silico prediction tools for new missense and splicing variants, following that it performed cosegregation data in the family. The variants were confirmed by Sanger sequencing using specific primers. Results: Molecular study of NGS and following sanger sequencing showed two variants in different CRB1 and AHI1 genes in the patients of family. In the study in proband (VI:2) revealed a homozygous frameshift variant in the exon 6 of the CRB1 gene (NM_201253.2; c.1576C>T; p. (Arg526*)) and in other member of the family a homozygous missense variant in the exon 15 of the AHI1 gene. Patients affected to LCA and a patient affected to Joubert syndrome (JBTS) presented different clinical features. Conclusions: In the present study. NGS is considered as the most new and powerful sequencing technique to detect causal variants in different genes. In the family identified two different molecular genetic characteristics of patients with (LCA) and mild JBTS which is involved retinal degeneration which are known to cause severe inherited retinal dystrophies.
VL  - 2
IS  - 1
ER  -

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