A novel truncating variant in the FGD1 gene associated with Aarskog-Scott syndrome in a family previously diagnosed with Tel Hashomer camptodactyly

Irena Kessel; Alina German; Amir Peleg; Regeneron Genetics Center; Claudia Gonzaga-Jauregui; Tamar Paperna; Nina Ekhilevitch; Alina Kurolap; Hagit Baris Feldman; Lena Sagi-Dain

doi:10.1002/ajmg.a.62401

A novel truncating variant in the FGD1 gene associated with Aarskog-Scott syndrome in a family previously diagnosed with Tel Hashomer camptodactyly

Am J Med Genet A. 2021 Oct;185(10):3161-3166. doi: 10.1002/ajmg.a.62401. Epub 2021 Jun 19.

Authors

Irena Kessel^{1

2}, Alina German^{2

3}, Amir Peleg⁴; Regeneron Genetics Center; Claudia Gonzaga-Jauregui⁵, Tamar Paperna⁶, Nina Ekhilevitch⁶, Alina Kurolap⁷, Hagit Baris Feldman^{7

8}, Lena Sagi-Dain^{2

4}

Affiliations

¹ Department of Neonatology, Carmel Medical Center, Haifa, Israel.
² Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
³ Pediatric Endocrinology, Bnei Zion Medical Center, Haifa, Israel.
⁴ Genetics Institute, Carmel Medical Center, Haifa, Israel.
⁵ Regeneron Genetics Center, Tarrytown, New York, USA.
⁶ The Genetics Institute, Rambam Health Care Campus, Haifa, Israel.
⁷ The Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
⁸ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

PMID: 34145742
DOI: 10.1002/ajmg.a.62401

Abstract

Tel Hashomer camptodactyly syndrome is a long-known entity characterized by camptodactyly with muscular hypoplasia, skeletal dysplasia, and abnormal palmar creases. Currently, the genetic basis for this disorder is unknown, thus there is a possibility that this clinical presentation may be contained within another genetic diagnosis. Here, we present a multiplex family with a previous clinical diagnosis of Tel Hashomer camptodactyly syndrome. Whole exome sequencing and pedigree-based analysis revealed a novel hemizygous truncating variant c.269_270dup (p.Phe91Alafs*34) in the FGD1 gene (NM_004463.3) in all three symptomatic patients, congruous with a diagnosis of Aarskog-Scott syndrome. Our report adds to the limited data on Aarskog-Scott syndrome, and emphasizes the importance of unbiased comprehensive molecular testing toward establishing a diagnosis for genetic syndromes with unknown genetic basis.

Keywords: Aarskog-Scott syndrome; genetic diseases; whole exome sequencing.

Publication types

Case Reports

MeSH terms

Diagnosis, Differential
Dwarfism / diagnosis*
Dwarfism / genetics
Dwarfism / pathology
Exome Sequencing
Face / abnormalities*
Face / pathology
Female
Genetic Diseases, X-Linked / diagnosis*
Genetic Diseases, X-Linked / genetics
Genetic Diseases, X-Linked / pathology
Genetic Predisposition to Disease*
Genitalia, Male / abnormalities*
Genitalia, Male / pathology
Guanine Nucleotide Exchange Factors / genetics*
Hand Deformities, Congenital / diagnosis*
Hand Deformities, Congenital / genetics
Hand Deformities, Congenital / pathology
Heart Defects, Congenital / diagnosis*
Heart Defects, Congenital / genetics
Heart Defects, Congenital / pathology
Heart Septal Defects, Atrial / diagnosis*
Heart Septal Defects, Atrial / genetics
Hirsutism / diagnosis*
Hirsutism / genetics
Humans
Limb Deformities, Congenital
Male
Muscular Diseases / diagnosis*
Muscular Diseases / genetics
Pedigree

Substances

FGD1 protein, human
Guanine Nucleotide Exchange Factors

Supplementary concepts

Aarskog Syndrome
Tel Hashomer camptodactyly syndrome