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A novel missense mutation in the NSDHL gene identified in a Lithuanian family by targeted next-generation sequencing causes CK syndrome

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Preiksaitiene E
  • Caro A
  • Benušiene E
  • Oltra S
  • Morkuniene A
  • Roselló MP
  • Kasnauskiene J
  • Monfort S
  • Kucinskas V
  • Mayo S

Grupos

Abstract

The NSDHL gene encodes 3-hydroxysteroid dehydrogenase involved in one of the later steps of the cholesterol biosynthetic pathway. Mutations in this gene can cause CHILD syndrome (OMIM 308050) and CK syndrome (OMIM 300831). CHILD syndrome is an X-linked dominant, male lethal disorder caused by mutations in the NSDHL gene that result in the loss of the function of the NSDHL protein. CK syndrome is an allelic X-linked recessive disorder. So far, 13 patients with CK syndrome from two families have been reported on. We present a new five-generation family with affected males manifesting clinical features of CK syndrome. Next generation sequencing was targeted to a custom panel of 542 genes with known or putative implication on intellectual disability. Missense mutation p.Gly152Asp was identified in the NSDHL gene in the DNA sample of the affected male. Mutation carrier status was confirmed for all the obligate carriers in the family. The clinical features of the affected males in the family manifested as weak fetal movements, severe intellectual disability, seizures, spasticity, atrophy of optic discs, microcephaly, plagiocephaly, skeletal abnormalities, and minor facial anomalies, including a high nasal bridge, strabismus, and micrognathia. A highly significant preferential transmission of the mutation was observed in this and previous families segregating CK syndrome. Our report expands the clinical spectrum of this syndrome to include weak fetal movements, spasticity, and plagiocephaly, and transmission ratio distortion. The various findings in these patients increase our understanding of the diversity of the clinical presentation of cholesterol biosynthesis disorders. (c) 2015 Wiley Periodicals, Inc.

Datos de la publicación

ISSN/ISSNe:
1552-4825, 1552-4833

AMERICAN JOURNAL OF MEDICAL GENETICS PART A  WILEY-BLACKWELL

Tipo:
Article
Páginas:
1342-1348
Factor de Impacto:
1,117 SCImago ℠
Cuartil:
Q2 SCImago ℠

Citas Recibidas en Web of Science: 5

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Keywords

  • X-linked intellectual disability; CK syndrome; CHILD syndrome; NSDHL gene; p.Gly152Asp mutation

Proyectos asociados

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RD09/0076/00021 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

COMPREHENSIVE, INTEGRATIVE AND GENOMIC APPROACH TO THE UNDERSTANDING AND TREATMENT OF CANCER AND LEUKEMIA.

Investigador Principal: MIGUEL ÁNGEL SANZ ALONSO

PIE13/00046 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2014

LA RUTA DE LA OXITOCINA EN LOS TRASTORNOS DEL ESPECTRO AUTISTA: IMPORTANCIA DE LAS VARIANTES GENÉTICAS CON RELEVANCIA FUNCIONAL.

Investigador Principal: CARMEN ORELLANA ALONSO

2014_0056_CRC_ORELLANA . 2014

ABORDAJE GENÓMICO PARA LA IDENTIFICACIÓN DE NUEVOS GENES Y MÓDULOS FUNCIONALES RESPONSABLES DE DISCAPACIDAD INTELECTUAL GRAVE.

Investigador Principal: FRANCISCO MARTÍNEZ CASTELLANO

PI14/00350 . INSTITUTO DE SALUD CARLOS III . 2015

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