Pathogenic Variants in TUBGCP6 of Familial Microcephaly and Chorioretinopathy

Sultana MH Faradz; Peter Ivan Hadiprajitno; Rina Susanti Chen; Muhamad Rifqy Setyanto; Sefri Noventi Sofia; Pujo Widodo; Nicole de Leeuw; Alexander P.A. Stegmann; Bregje W van Bon

doi:10.31584/jhsmr.20251251

Authors

Sultana MH Faradz Genomic Research Center, Universitas YARSI, Jakarta 10510, Indonesia./ Genetic Counselor and Genomic Consultant, Prodia Laboratory, Jakarta 10430, Indonesia.
Peter Ivan Hadiprajitno Faculty of Medicine, Diponegoro University, Semarang 50275, Indonesia.
Rina Susanti Chen Genetic Counselor and Genomic Consultant, Prodia Laboratory, Jakarta 10430, Indonesia.
Muhamad Rifqy Setyanto Vitreoretinal Division, Department of Ophthalmology, Faculty of Medicine, Jenderal Soedirman University, Purwokerto 53122, Indonesia./ Department of Ophthalmology, Kasih Ibu Hospital, Surakarta 57412, Indonesia.
Sefri Noventi Sofia Department of Cardiology and Vascular Medicine, Faculty of Medicine, Diponegoro University, Semarang 50275, Indonesia.
Pujo Widodo ENT Department, Dr. Kariadi General Hospital, Semarang 50231, Indonesia.
Nicole de Leeuw Department of Human Genetics, Radboud University Medical Center, Nijmegen 6525, The Netherlands.
Alexander P.A. Stegmann Department of Human Genetics, Radboud University Medical Center, Nijmegen 6525, The Netherlands.
Bregje W van Bon Department of Human Genetics, Radboud University Medical Center, Nijmegen 6525, The Netherlands.

DOI:

https://doi.org/10.31584/jhsmr.20251251

Keywords:

autosomal recessive, chorioretinopathy, MCCRP1, microcephaly, TUBGCP6 gene

Abstract

Microcephaly and chorioretinopathy type 1 (MCCRP1) is an autosomal recessive syndrome characterized by severe microcephaly, facial dysmorphisms, chorioretinopathy, and developmental delays. This rare condition is caused by homozygous or compound heterozygous pathogenic variants in the Tubulin Gamma Complex Component 6 (TUBGCP6) gene. We present 2 siblings from a non-consanguineous family in Indonesia diagnosed with MCCRP1. Both had a history of intrauterine growth retardation (IUGR) and were born with microcephaly and low birth weight. They exhibited developmental delays and hyperactive behavior. Facial dysmorphisms included upslanting palpebral fissures, strabismus, long philtrum, and a low anterior hairline. Ophthalmologic examination revealed chorioretinopathy in both siblings, while cardiac and hearing evaluations were normal. Microarray analysis revealed no likely pathogenic copy number variants (CNVs). Whole exome sequencing (WES) was performed on DNA from the siblings and their parents. The variant analysis identified a paternal pathogenic splice variant c.2066-6A>G and a maternal pathogenic nonsense variant c.3393G>A in the TUBGCP6 gene (NM_020461.4) in both siblings, indicating a compound heterozygous variant. This is the first case report of familial MCCRP1 in Indonesia, presenting both clinical features and genetic analysis of the TUBGCP6 gene.

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