Mutations in KIAA0753 cause Joubert syndrome associated with growth hormone deficiency.
Hum Genet
; 136(4): 399-408, 2017 04.
Article
en En
| MEDLINE
| ID: mdl-28220259
ABSTRACT
Joubert syndrome and related disorders (JSRD) are a heterogeneous group of ciliopathies defined based on the mid-hindbrain abnormalities that result in the characteristic "molar tooth sign" on brain imaging. The core clinical findings of JSRD are hypotonia, developmental delay, abnormal eye movements and breathing abnormalities. To date, more than 30 JSRD genes that encode proteins important for structure and/or function of cilia have been identified. Here, we present 2 siblings with Joubert syndrome associated with growth hormone deficiency. Whole exome sequencing of the family identified compound heterozygous mutations in KIAA0753, i.e., a missense mutation (p.Arg257Gly) and an intronic mutation (c.2359-1G>C). The intronic mutation alters normal splicing by activating a cryptic acceptor splice site in exon 16. The novel acceptor site skips nine nucleotides, deleting three amino acids from the protein coding frame. KIAA0753 (OFIP) is a centrosome and pericentriolar satellite protein, previously not known to cause Joubert syndrome. We present comprehensive clinical descriptions of the Joubert syndrome patients as well as the cellular phenotype of defective ciliogenesis in the patients' fibroblasts.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Retina
/
Anomalías Múltiples
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Hormona del Crecimiento
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Cerebelo
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Anomalías del Ojo
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Enfermedades Renales Quísticas
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Proteínas Asociadas a Microtúbulos
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Mutación
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Hum Genet
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos