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Background <p>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.</p> Methods <p>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.</p> Results <p>Eighteen homozygous, three compound heterozygous, and two heterozygous variants were present in thirteen patients. <i>AHI1,</i> c.961dupG, p.Asp321fs*5; <i>CPLANE1</i>, c.569A &gt; G, p.Glu190Gly; <i>CPLANE1</i>, c.7495dup, Ile2499Asnfs*2; <i>CC2D2A</i>, c.4143G &gt; T, p.Lys1381Asn; <i>KIAA0586</i>, c.4889&#xa0;T &gt; C, p.Leu1630Pro; <i>PIBF1</i>, c.1231C &gt; T, p.Arg411Ter; <i>TMEM237,</i> c.591delG, p.Thr198Profs*5; <i>TMEM138,</i> c.376G &gt; C, p.Ala126Pro were novel variants. In addition, in the OGM analysis, a heterozygous insertion was detected in the 3’UTR region of <i>RPGRIP1L</i>. Patients with a diagnosis of JS that could not be explained by WES itself but could be explained together with OGM were discussed.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年5月31日

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  • Aslihan Kiraz,
  • Murat Erdogan,
  • Burhan Balta,
  • Hakan Gumus,
  • Mehmet Burak Mutlu,
  • Nurana Mammadova,
  • Firat Ozcelik,
  • Izem Olcay Sahin,
  • Ahmet Sami Guven,
  • Sefer Kumandas,
  • Ahmet Savranlar,
  • Filiz Karaman,
  • Huseyin Per,
  • Munis Dundar

摘要

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.