TY - JOUR
T1 - Novel KIAA1033/WASHC4 mutations in three patients with syndromic intellectual disability and a review of the literature
AU - Assoum, Mirna
AU - Bruel, Ange Line
AU - Crenshaw, Melissa L.
AU - Delanne, Julian
AU - Wentzensen, Ingrid M.
AU - McWalter, Kirsty
AU - Dent, Karin M.
AU - Vitobello, Antonio
AU - Kuentz, Paul
AU - Thevenon, Julien
AU - Duffourd, Yannis
AU - Thauvin-Robinet, Christel
AU - Faivre, Laurence
N1 - Funding Information:
We wish to thank the subjects and families involved in the study, the “Centre de Calcul” of the University of Burgundy (CCUB) for their technical support and management of the bioinformatics platform. This work was supported by the “Conseil Régional de Bourgogne” through the “plan d'actions régional pour l'innovation (PARI 2016)” and the European Union through the PO FEDER-FSE Bourgogne 2014/2020 programs. Several author(s) of this publication are members of the European Reference Network for Developmental Anomalies and Intellectual Disability (ERN-ITHACA).
Funding Information:
We wish to thank the subjects and families involved in the study, the “Centre de Calcul” of the University of Burgundy (CCUB) for their technical support and management of the bioinformatics platform. This work was supported by the “Conseil Régional de Bourgogne” through the “plan d'actions régional pour l'innovation (PARI 2016)” and the European Union through the PO FEDER‐FSE Bourgogne 2014/2020 programs. Several author(s) of this publication are members of the European Reference Network for Developmental Anomalies and Intellectual Disability (ERN‐ITHACA).
Publisher Copyright:
© 2020 Wiley Periodicals, Inc.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - In 2011, KIAA1033/WASHC4 was associated with autosomal recessive intellectual disability (ARID) in a large consanguineous family comprising seven affected individuals with moderate ID and short stature. Since then, no other cases of KIAA1033 variants have been reported. Here we describe three additional patients (from two unrelated families) with syndromic ID due to compound heterozygous KIAA1033 variants ascertained by exome sequencing (ES). Two sisters, aged 4 and 5.5 years, had a stop-gain and a missense variants, each inherited from one parent (p.(Gln442*) and p.(Asp1048Gly)). Both had learning disabilities, macrocephaly, dysmorphic features, skeletal anomalies, and subependymal heterotopic nodules. In addition, the younger sibling had a congenital absence of the right internal carotid and bilateral sensorineural hearing loss. The third patient was aged 34 years and had two missense variants, one inherited from each parent (p.(Lys1079Arg) and p.(His503Arg)). This patient presented with mild ID, short stature, and microcephaly. KIAA1033 encodes a large protein (WASHC4), which is part of the WASH complex. The WASH complex is involved in the regulation of the fission of tubules that serve as transport intermediates during endosome sorting. Another member of the WASH complex, KIAA0196/WASHC5, has already been implicated in ARID with brain and cardiac malformations, under the designation of 3C or Ritscher-Schinzel syndrome (MIM#20210). ES has proved efficient for finding replications of genes with insufficient data in the literature to be defined as new OMIM genes. We conclude that KIAA1033 is responsible for a heterogeneous ARID phenotype, and additional description will be needed to refine the clinical phenotype.
AB - In 2011, KIAA1033/WASHC4 was associated with autosomal recessive intellectual disability (ARID) in a large consanguineous family comprising seven affected individuals with moderate ID and short stature. Since then, no other cases of KIAA1033 variants have been reported. Here we describe three additional patients (from two unrelated families) with syndromic ID due to compound heterozygous KIAA1033 variants ascertained by exome sequencing (ES). Two sisters, aged 4 and 5.5 years, had a stop-gain and a missense variants, each inherited from one parent (p.(Gln442*) and p.(Asp1048Gly)). Both had learning disabilities, macrocephaly, dysmorphic features, skeletal anomalies, and subependymal heterotopic nodules. In addition, the younger sibling had a congenital absence of the right internal carotid and bilateral sensorineural hearing loss. The third patient was aged 34 years and had two missense variants, one inherited from each parent (p.(Lys1079Arg) and p.(His503Arg)). This patient presented with mild ID, short stature, and microcephaly. KIAA1033 encodes a large protein (WASHC4), which is part of the WASH complex. The WASH complex is involved in the regulation of the fission of tubules that serve as transport intermediates during endosome sorting. Another member of the WASH complex, KIAA0196/WASHC5, has already been implicated in ARID with brain and cardiac malformations, under the designation of 3C or Ritscher-Schinzel syndrome (MIM#20210). ES has proved efficient for finding replications of genes with insufficient data in the literature to be defined as new OMIM genes. We conclude that KIAA1033 is responsible for a heterogeneous ARID phenotype, and additional description will be needed to refine the clinical phenotype.
KW - KIAA1033/WASHC4
KW - exome sequencing
KW - intellectual disability
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UR - http://www.scopus.com/inward/citedby.url?scp=85078246129&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.61487
DO - 10.1002/ajmg.a.61487
M3 - Article
C2 - 31953988
AN - SCOPUS:85078246129
SN - 1552-4825
VL - 182
SP - 792
EP - 797
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 4
ER -