Received: 11 February 2020 Revised: 2 July 2020 Accepted: 2 July 2020
DOI: 10.1111/ahg.12401
ORIGINAL ARTICLE
Clinical and exome sequencing findings in seven children
with Bardet–Biedl syndrome from Turkey
Evren Gumus
1, 2
Ebru Tuncez
3
Ozlem Oz
1
Merve Saka Guvenc
4
1
Department of Medical Genetics, Faculty
of Medicine, University of Harran,
Sanliurfa, Turkey
2
Department of Medical Genetics,
Faculty of Medicine, University of Mugla
Sitki Kocman, Mugla, Turkey
3
Clinic of Medical Genetics, Sanliurfa
Training and Research Hospital,
Sanliurfa, Turkey
4
Genetic Diagnosis Center, Tepecik
Training and Research Hospital,
University of Health Sciences, Izmir,
Turkey
Correspondence
Evren Gumus, MD, Faculty of Medicine,
Department of Medical Genetics, Univer-
sity of Mugla Sitki Kocman, Mugla, Turkey.
Email: evreng@ymail.com
Abstract
Background: Bardet–Biedl syndrome (BBS) is a very-rare autosomal recessive
genetic disorder with severe multisystem manifestations. Genetic testing plays
an important role in the early diagnosis of the disease. In this study, while trying
to elucidate the genetic etiology of seven individuals with clinical BBS diagno-
sis from six different families, we also aimed to examine the distribution of BBS
variations in this region of Turkey.
Methods and materials: Exome sequencing analysis is performed for clinically
diagnosed patients with BBS in the present study followed by parental segrega-
tion. The unreported and previously described clinical features are presented.
Results: Homozygous variants, four of which are unreported, in BBS-related
genes (BBS5 [c.682-2A > G], MKKS [c.775del], BBS7 [c.849+1G > T], BBS9
[c.965G > A], BBS10 [c.145C > T], LZTFL1[c.384G > A]) are detected for all the
seven individuals included in the study. The most common clinical finding is
polydactyly followed by renal anomalies. The clinical features not previously
described are correlated to the unreported variant.
Conclusions: In this study, exome sequencing findings are discussed and four
previously unreported disease-associated variants are described including the
fifth BBS-implicated LZTFL1 change and possible genotype–phenotype correla-
tion is described.
KEYWORDS
Bardet–Biedl Syndrome, BBS, exome sequencing, LZTFL1, variant
1 INTRODUCTION
Bardet–Biedl syndrome (BBS) is a very rare autosomal
recessive genetic disorder with severe multisystem mani-
festations. The syndrome is characterized primarily by rod-
cone dystrophy, postaxial polydactyly, obesity, intellectual
disability, hypogonadism/genital abnormalities and renal
anomalies; and secondarily by speech disorder, develop-
mental delay, behavioral abnormalities, eye anomalies,
brachydactyly/syndactyly, ataxia, hypertonia, anosmia,
oral and dental abnormalities, cardiac anomalies, hepatic
involvement, dysmorphism, Hirschsprung disease, and
diabetes mellitus. The presence of four primary findings
or three primary findings and two secondary findings is
diagnostic (Beales et al., 2001; Beales, Elcioglu, Woolf,
Parker, & Flinter, 1999; Billingsley et al., 2010; Forsythe
& Beales, 2013; Warburg & Riise, 2000). According to the
diagnostic criteria, it is not always possible to diagnose
this syndrome at an early age, the most important reason
for this is that some findings such as obesity, rod-cone dys-
trophy, anosmia, and behavioral abnormalities manifest
as the age progresses. In this context, genetic tests play
Ann Hum Genet. 2020;1–10. © 2020 John Wiley & Sons Ltd/University College London 1 wileyonlinelibrary.com/journal/ahg