Case Report: A Novel In-Frame Deletion of GLIS2 Leading to Nephronophthisis and Early Onset Kidney Failure

Variants in the GLIS family zinc finger protein 2 (GLIS2) are a rare cause of nephronophthisis-related ciliopathies (NPHP-RC). A reduction in urinary concentration and a progressive chronic tubulointerstitial nephropathy with corticomedullary cysts are the major characteristic features of NPHP. NPHP demonstrates phenotypic and genetic heterogeneity with at least 25 different recessive genes associated with the disease. We report a female, from a consanguineous family, who presented age 9 years with echogenic kidneys with loss of cortico-medullary differentiation and progressive chronic kidney disease reaching kidney failure by 10 years of age. A novel homozygous in-frame deletion (NM_032,575.3: c.560_574delACCATGTCAACGATT, p.H188_Y192del) in GLIS2 was identified using whole exome sequencing (WES) that segregated from each parent. The five amino acid deletion disrupts the alpha-helix of GLIS2 zinc-finger motif with predicted misfolding of the protein leading to its predicted pathogenicity. This study broadens the variant spectrum of GLIS2 variants leading to NPHP-RC. WES is a suitable molecular tool for children with kidney failure suggestive of NPHP-RC and should be part of routine diagnostics in kidney failure of unknown cause, especially in consanguineous families.

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Mutations in a zinc finger protein causing a novel autosomal recessive mental retardation syndrome identified through homozygosity mapping and whole exome sequencing of a single affected individual

Qatar Foundation Annual Research Forum Proceedings ◽

10.5339/qfarf.2012.bmo9 ◽

2012 ◽

pp. BMO9

Author(s):

Marios Kambouris ◽

Tawfeg Ben-Omran ◽

Yasser Al-Sarraj ◽

Rehab Ali ◽

Khaoula Erraffi ◽

...

Keyword(s):

Mental Retardation ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Zinc Finger ◽

Autosomal Recessive ◽

Zinc Finger Protein ◽

Homozygosity Mapping ◽

Affected Individual ◽

Finger Protein ◽

Whole Exome

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A Novel Gene ZNF862 Causes Hereditary Gingival Fibromatosis

10.1101/2020.04.27.20080804 ◽

2020 ◽

Author(s):

Juan Wu ◽

Dongna Chen ◽

Hui Huang ◽

Ning Luo ◽

Huishuang Chen ◽

...

Keyword(s):

Zinc Finger ◽

Autosomal Dominant ◽

Zinc Finger Protein ◽

Physiological Role ◽

Chinese Family ◽

Inheritance Pattern ◽

Dominant Inheritance ◽

Finger Protein ◽

Whole Exome ◽

Gingival Fibromatosis

Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis which is featured as a localized or generalized overgrowth of gingivae. HGF is genetically heterogeneous and usually be transmitted as an autosomal-dominant inheritance pattern, also can be as autosomal-recessive or occur sporadically. Currently only two genes (SOS1 and REST), as well as four loci (2p22.1, 2p23.3-p22.3, 5q13-q22, and 11p15), have been identified as associated with HGF in a dominant inheritance pattern. Here we report thirteen individuals with autosomal-dominant non-syndromic HGF from a large four-generation Chinese family. Whole-exome sequencing followed by further genetic co-segregation analysis was performed for the family members across three generations. A novel heterozygous missense mutation (NM_001099220.3: c.2812G>A) in zinc finger protein 862 gene (ZNF862) was identified, and it is absent among the population as reported from the Genome Aggregation Database, Exome Aggregation Consortium (ExAC) and 1000 Genomes. ZNF862 is a predicted intracellular protein which function is not yet identified, as a zinc finger protein it may be involved in transcriptional regulation. ZNF862 is expressed ubiquitously across tissues, it may play various roles under different physiological condition. Here for the first time we identify the physiological role of ZNF862 for the association with the HGF trait.

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