Homozygosity for a novel missense variant of RPGRIP1L causing Joubert syndrome with renal defects in a family of Chinese descent

Objective. To diagnose and explore the genetic cause of Joubert syndrome (JS) in a fetus. Methods. Prenatal ultrasound and magnetic resonance imaging (MRI) examinations were performed, and genetic analysis was conducted using targeted next-generation sequencing (NGS) and Sanger sequencing. Results. Prenatal ultrasound and MRI examinations showed cerebellar vermis hypoplasia and molar tooth sign (MTS); hence the fetus was diagnosed with JS. Further genetic analysis revealed a known missense variant (c.3599C>T, p.A1200V) and a novel missense variant (c.3857G>A, p.R1286H) in the C5orf42 gene of the fetus. Conclusion. Our study provides insights into prenatal and early diagnosis of JS and expands the variation spectrum of C5orf42 gene.

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A Homozygous Missense Variant in INPP5E Associated with Joubert Syndrome and Related Disorders

Molecular Syndromology ◽

10.1159/000479673 ◽

2017 ◽

Vol 8 (6) ◽

pp. 313-317 ◽

Cited By ~ 2

Author(s):

Mitesh Shetty ◽

Nimmy Ramdas ◽

Shubhi Sahni ◽

Nandita Mullapudi ◽

Sridevi Hegde

Keyword(s):

Missense Variant ◽

Joubert Syndrome

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A Novel Homozygous Variant of TMEM231 in a Case With Hypoplasia of the Cerebellar Vermis and Polydactyly

Frontiers in Pediatrics ◽

10.3389/fped.2021.774575 ◽

2021 ◽

Vol 9 ◽

Author(s):

Tao Wang ◽

Yu-Xing Liu ◽

Fang-Mei Luo ◽

Yi Dong ◽

Ya-Li Li ◽

...

Keyword(s):

Plasma Membrane ◽

Genetic Counseling ◽

Transmembrane Protein ◽

Missense Variant ◽

Joubert Syndrome ◽

Cerebellar Vermis ◽

Healthy Controls ◽

Genetic Lesion ◽

Whole Exome ◽

Novel Variant

Background: Transmembrane protein 231 (TMEM231) is a component of the B9 complex that participates in the formation of the diffusion barrier between the cilia and plasma membrane. Mutations in TMEM231 gene may contribute to the Joubert syndrome (JBTS) or Meckel–Gruber syndrome (MKS). However, reports on JBTS or MKS caused by TMEM231 mutations are comparatively rare.Method: We describe a Chinese fetus with unexplained hypoplasia of the cerebellar vermis and polydactyly, detected by ultrasound imaging. The fetus was primarily diagnosed with JBTS/MKS. The parents of this fetus were non-consanguineous and healthy. Whole-exome sequencing (WES) and bioinformatics strategies were employed to explore the genetic lesion of this family.Results: An unknown missense variant (c.19C>T;p.R7W) of TMEM231 gene was detected. The variant was predicted as pathogenic and was absent in our 200 healthy controls.Conclusion: WES was employed to explore the genetic lesion of a fetus with unexplained hypoplasia of the cerebellar vermis and polydactyly. A novel variant in TMEM231 gene was identified. Our study not only provided data for genetic counseling and prenatal diagnosis to this family but also broadened the spectrum of TMEM231 mutations.

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Joubert syndrome: long-term follow-up

Developmental Medicine & Child Neurology ◽

10.1017/s0012162204001161 ◽

2004 ◽

Vol 46 (10) ◽

Cited By ~ 2

Author(s):

Peter R Hodgkins ◽

Christopher M Harris ◽

Fatima S Shawkat ◽

Dorothy A Thompson ◽

Kling Chong ◽

...

Keyword(s):

Joubert Syndrome ◽

Long Term Follow Up

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Three Cases of Joubert Syndrome in a Consanguineous Syrian Family and a Interesting Case of Multinational Collaboration

Journal of Pediatric Genetics ◽

10.1055/s-0040-1721826 ◽

2021 ◽

Author(s):

Davor Petrović ◽

Vida Čulić ◽

Zofia Swinderek-Alsayed

Keyword(s):

Low Income ◽

Autosomal Recessive ◽

Autosomal Recessive Disorder ◽

Joubert Syndrome ◽

Interesting Case ◽

Low Income Countries ◽

Ocular Motor ◽

Quality Health Care ◽

Quality Health ◽

Motor Apraxia

AbstractJoubert syndrome (JS) is a rare congenital, autosomal recessive disorder characterized by a distinctive brain malformation, developmental delay, ocular motor apraxia, breathing abnormalities, and high clinical and genetic heterogeneity. We are reporting three siblings with JS from consanguineous parents in Syria. Two of them had the same homozygous c.2172delA (p.Trp725Glyfs*) AHI1 mutation and the third was diagnosed prenatally with magnetic resonance imaging. This pathogenic variant is very rare and described in only a few cases in the literature. Multinational collaboration could be of benefit for the patients from undeveloped, low-income countries that have a low-quality health care system, especially for the diagnosis of rare diseases.

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