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Klin Padiatr 2021; 233(02): 53-58
DOI: 10.1055/a-1223-2489
Original Article

Greig Cephalopolysyndactyly Syndrome: Phenotypic Variability Associated with Variants in Two Different Domains of GLI3

Greig-Zephalopolysyndaktylie-Syndrom: Phänotypische Variabilität geht mit Varianten in zwei verschiedenen Domänen von GLI3 einher
Hammal Khan
1   Department of Biosciences, COMSATS University, Islamabad, Pakistan
,
Abdullah,
Sohail Ahmed
3   Institute of Biochemistry, University of Balochistan, Quetta, Pakistan
,
Sadia Nawaz
4   Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan
,
Wasim Ahmad
2   Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
,
Muhammad Arshad Rafiq
1   Department of Biosciences, COMSATS University, Islamabad, Pakistan
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Abstract

Background GLI3 is a transcriptional regulator of several genes involved in mammalian skeletal development. Mutations in the pleiotropic gene GLI3 may result in different inherited disorders including Greig cephalopolysyndactyly syndrome (GCPS). GCPS is characterized by mild to severe craniofacial and limb malformations.

Methods and Results Here, we report clinical and molecular study of 3 families with GCPS originated in different regions of Pakistan. Sanger sequencing revealed two novel variants including a frameshift [c. 3790_3791InsC, p.(Gly1236Argfs*11)] and a missense [c.1692A>G, p.(His536Arg)], and one previously reported variant [c.1965_1966delAT, p.(His627Glufs*48)] located in 2 different domains of the GLI3.

Conclusion This study not only expanded spectrum of the mutations in the GLI3 but also highlighted phenotypic variability in the GCPS patients. This will facilitate diagnosis and genetic counseling of families with same and related disorders in the Pakistani population.

Zusammenfassung

Hintergrund GLI3 ist ein Transkriptionsregulator von mehreren Genen mit Einfluss auf die Skelettentwicklung bei Säugetieren. Mutationen im pleiotropen Gen GLI3 können verschiedene Erbkrankheiten zur Folge haben. Eine dieser Krankheiten ist das Greig-Zephalopolysyndaktylie-Syndrom (GCPS), das durch leichte bis schwere Missbildungen des Gesichtsschädels und der Extremitäten charakterisiert ist.

Methodik und ErgebnisseWir berichten über eine klinische und molekulare Studie zu drei Familien mit GCPS, die aus verschiedenen Regionen Pakistans stammten. Die Sanger-Sequenzierung fand zwei neuartige Varianten, ein Frameshift [c. 3790_3791InsC, p.(Gly1236Argfs* 11)] und eine Missense [c.1692A > G, p.(His536Arg)], sowie eine bereits berichtete Variante [c.1965_1966delAT, p.(His-627Glufs*48)], die auf zwei verschiedenen Domänen von GLI3 gelegen sind.

SchlussfolgerungDie vorliegende Studie erweiterte nicht nur das Spektrum der detektierten Mutationen im GLI3-Gen, sondern machte auch die phänotypische Variabilität bei GCPS-Patienten deutlich. Dadurch wird die Diagnostik und humangenetische Beratung von Familien mit diesem Syndrom und verwandten Störungen in der pakistanischen Bevölkerung erleichtert.

Key words

GLI3 - Greig cephalopolysyndactyly syndrome - Novel variants - Phenotypic variability - Sanger sequencing

Schlüsselwörter

GLI3 - Greig-Zephalopolysyndaktylie-Syndrom - neuartige Varianten - phänotypische Variabilität - Sanger-Sequenzierung


Publication History

Article published online:
18 December 2020

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