Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 31;26(1):47.
doi: 10.1007/s10048-025-00825-8.

A case series of joubert syndrome evaluated with whole exome sequencing and the utility of optical genome mapping in the diagnosis

Aslihan Kiraz  1 , Murat Erdogan  2 , Burhan Balta  2 , Hakan Gumus  3 , Mehmet Burak Mutlu  4 , Nurana Mammadova  5 , Firat Ozcelik  5 , Izem Olcay Sahin  5 , Ahmet Sami Guven  6 , Sefer Kumandas  3 , Ahmet Savranlar  7 , Filiz Karaman  8 , Huseyin Per  3 , Munis Dundar  5
Affiliations

A case series of joubert syndrome evaluated with whole exome sequencing and the utility of optical genome mapping in the diagnosis

Aslihan Kiraz et al. Neurogenetics. .

Abstract

Background: Joubert syndrome (JS) is a rare autosomal recessive genetic disease characterized by molar tooth sign, hypotonia during infancy, developmental delay, and/or intellectual disability. Over 40 genes have been associated with the syndrome, and population-specific founder variants have been defined.

Methods: In our study, we evaluated 34 patients with clinical, radiological, and laboratory findings. Whole exome sequencing (WES) analysis was performed on all patients to explain the underlying genetic causes. Optical genome mapping (OGM) was performed to elucidate the genetic mechanism in two patients with heterozygous variants after WES analysis.

Results: Eighteen homozygous, three compound heterozygous, and two heterozygous variants were present in thirteen patients. AHI1, c.961dupG, p.Asp321fs*5; CPLANE1, c.569A > G, p.Glu190Gly; CPLANE1, c.7495dup, Ile2499Asnfs*2; CC2D2A, c.4143G > T, p.Lys1381Asn; KIAA0586, c.4889 T > C, p.Leu1630Pro; PIBF1, c.1231C > T, p.Arg411Ter; TMEM237, c.591delG, p.Thr198Profs*5; TMEM138, c.376G > C, p.Ala126Pro were novel variants. In addition, in the OGM analysis, a heterozygous insertion was detected in the 3'UTR region of RPGRIP1L. Patients with a diagnosis of JS that could not be explained by WES itself but could be explained together with OGM were discussed.

Conclusion: This study contributes to the clinical and molecular characteristics of JS patients. Despite growing literature about JS, this is the first study to use OGM for the diagnosis.

Keywords: Case series; Exome sequencing; Joubert syndrome; Optical genome mapping.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Erciyes University Local Ethics Committee (Ethical number: 2017/281 and 2024/122). All patients and/or parents gave written informed consent. Conflict of interest: The authors declare no competing interests.

References

    1. Parisi M, Glass I. Joubert Syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle;, Seattle (WA): GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2019.
    1. Parisi MA (2019) The molecular genetics of Joubert syndrome and related ciliopathies: The challenges of genetic and phenotypic heterogeneity. Transl Sci rare Dis 4:25–49 - PubMed - PMC
    1. Incecik F, Hergüner MÖ, Altunbaşak Ş, Gleeson JG (2012) Joubert syndrome: Report of 11 cases. Turk J Pediatr 54:605–611 - PubMed - PMC
    1. Poretti A, Snow J, Summers AC, Tekes A, Huisman TAGM, Aygun N, Carson KA, Doherty D, Parisi MA, Toro C, Yildirimli D, Vemulapalli M, Mullikin JC, Cullinane AR, Vilboux T, Gahl WA, Gunay-Aygun M (2017) Joubert syndrome: Neuroimaging findings in 110 patients in correlation with cognitive function and genetic cause. J Med Genet 54:521–529 - PubMed - DOI
    1. Serpieri V, D’Abrusco F, Dempsey JC, Cheng Y-HH, Arrigoni F, Baker J, Battini R, Bertini ES, Borgatti R, Christman AK, Curry C, D’Arrigo S, Fluss J, Freilinger M, Gana S, Ishak GE, Leuzzi V, Loucks H, Manti F, Mendelsohn N, Merlini L, Miller CV, Muhammad A, Nuovo S, Romaniello R, Schmidt W, Signorini S, Siliquini S, Szczałuba K, Vasco G, Wilson M, Zanni G, Boltshauser E, Doherty D, Valente EM (2022) SUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum. J Med Genet 59:888–894 - PubMed - DOI

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources