Format

Send to

Choose Destination
J Med Genet. 2017 Dec;54(12):830-835. doi: 10.1136/jmedgenet-2017-104748. Epub 2017 Oct 26.

Expanding the clinical spectrum of recessive truncating mutations of KLHL7 to a Bohring-Opitz-like phenotype.

Author information

1
Inserm UMR 1231 GAD Team, Genetics of Developmental Anomalies, Université de Bourgogne-Franche Comté, Dijon, France.
2
FHU-TRANSLAD, Université de Bourgogne/CHU, Dijon, France.
3
Department of Reproduction and Growth, UOL of Medical Genetics, University Hospital St Anna, Ferrara, Italy.
4
Department of Medical Science, UOL of Medical Genetics, University Hospital St Anna, Ferrara, Italy.
5
Clinical Genetics Department, University Hospitals Bristol NHS Foundation Trust, St Michael's Hospital, Bristol, UK.
6
University of Bristol, Glasgow, UK.
7
Department of Clinical Genetics, Queen Elizabeth University Hospital, Glasgow, UK.
8
Bristol Genetics Laboratory, Southmead Hospital, Bristol, UK.
9
Department of Human Genetics, McGill University Health Centre, Montreal, Canada.
10
Department of Reproduction and Growth, Neonatal Intensive Care Unit, University Hospital St Anna, Ferrara, Italy.
11
Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands.
12
Institute of Human Genetics, Westfälische Wilhelms-Universität Münster, Münster, Germany.
13
Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, Évry, France.
14
Service de Génétique, Centre Hospitalier de Mulhouse, Mulhouse, Alsace, France.
15
Wellcome Trust Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
16
Centre de Génétique, Hôpital Couple Enfant, CHU de Grenoble Alpes, La Tronche, France.

Abstract

BACKGROUND:

Bohring-Opitz syndrome (BOS) is a rare genetic disorder characterised by a recognisable craniofacial appearance and a typical 'BOS' posture. BOS is caused by sporadic mutations ofASXL1. However, several typical patients with BOS have no molecular diagnosis, suggesting clinical and genetic heterogeneity.

OBJECTIVES:

To expand the phenotypical spectrum of autosomal recessive variants of KLHL7, reported as causing Crisponi syndrome/cold-induced sweating syndrome type 1 (CS/CISS1)-like syndrome.

METHODS:

We performed whole-exome sequencing in two families with a suspected recessive mode of inheritance. We used the Matchmaker Exchange initiative to identify additional patients.

RESULTS:

Here, we report six patients with microcephaly, facial dysmorphism, including exophthalmos, nevus flammeus of the glabella and joint contractures with a suspected BOS posture in five out of six patients. We identified autosomal recessive truncating mutations in the KLHL7 gene. KLHL7 encodes a BTB-kelch protein implicated in the cell cycle and in protein degradation by the ubiquitin-proteasome pathway. Recently, biallelic mutations in the KLHL7 gene were reported in four families and associated with CS/CISS1, characterised by clinical features overlapping with our patients.

CONCLUSION:

We have expanded the clinical spectrum of KLHL7 autosomal recessive variants by describing a syndrome with features overlapping CS/CISS1 and BOS.

KEYWORDS:

Bohring-Opitz like syndrome; klhl7; whole exome sequencing

PMID:
29074562
DOI:
10.1136/jmedgenet-2017-104748
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center