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Further refinement of the critical minimal genetic region for the imprinting disorder 6q24 transient neonatal diabetes

Further refinement of the critical minimal genetic region for the imprinting disorder 6q24 transient neonatal diabetes
Further refinement of the critical minimal genetic region for the imprinting disorder 6q24 transient neonatal diabetes
AIMS/HYPOTHESIS: Transient neonatal diabetes (TND) is associated with overexpression of genes within a critical region on 6q24. This study aims to refine the boundaries of this region to reduce the number of potential candidate genes for 6q24 TND.

METHODS: Fifteen patients with transient neonatal diabetes and submicroscopic chromosome 6 duplications were investigated. The duplications were confirmed by microsatellite analysis and subsequently mapped using tiled chromosome 6 array Comparative Genomic Hybridisation (aCGH) and MLPA. Duplication boundaries were compared to identify the minimal shared region of duplication. These data were then used with available clinical data to identify associations between size of 6q24 duplication and severity of TND phenotype.

RESULTS: Alignment of the minimal region of duplication to the human genome reduced the minimal TND critical region, formerly estimated at 440 kb, to 160-173 kb, revealing PLAGL1 (pleiomorphic adenoma gene-like 1) and HYMAI (imprinted in hydatidiform mole) to be the only genes wholly included therein. Additionally, the complete paternal duplication of a region containing the theoretical protein FAM164B was associated with the severe growth restriction observed in 6q24 duplication patients.

CONCLUSIONS/INTERPRETATION: This study has significantly reduced the critical region associated with 6q24 TND. It has eliminated several previous TND candidate genes, leaving the overlapping imprinted genes PLAGL1 and HYMAI as the only remaining complete candidate genes for 6q24 TND. Moreover, these data provide the first evidence that an additional region, encompassing the theoretical protein FAM164B, may have a critical role in the growth restriction phenotype observed in many 6q24 TND patients.
0012-186X
2347-2351
Docherty, L.E.
4accb565-e53b-400f-8d62-83935e2ae410
Poole, R
d8fe00fa-9deb-4a34-a7d8-4b7f57ce82fa
Mattocks, C.J.
2d943111-cfdf-4f0d-9ecc-0737e541fe36
Lehmann, A.
2a783c9a-b9b8-4b7f-b3ac-a0d487f16844
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Mackay, D.J.G.
588a653e-9785-4a00-be71-4e547850ee4a
Docherty, L.E.
4accb565-e53b-400f-8d62-83935e2ae410
Poole, R
d8fe00fa-9deb-4a34-a7d8-4b7f57ce82fa
Mattocks, C.J.
2d943111-cfdf-4f0d-9ecc-0737e541fe36
Lehmann, A.
2a783c9a-b9b8-4b7f-b3ac-a0d487f16844
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Mackay, D.J.G.
588a653e-9785-4a00-be71-4e547850ee4a

Docherty, L.E., Poole, R, Mattocks, C.J., Lehmann, A., Temple, I.K. and Mackay, D.J.G. (2010) Further refinement of the critical minimal genetic region for the imprinting disorder 6q24 transient neonatal diabetes. Diabetologia, 53 (11), 2347-2351. (doi:10.1007/s00125-010-1853-2). (PMID:20668833)

Record type: Article

Abstract

AIMS/HYPOTHESIS: Transient neonatal diabetes (TND) is associated with overexpression of genes within a critical region on 6q24. This study aims to refine the boundaries of this region to reduce the number of potential candidate genes for 6q24 TND.

METHODS: Fifteen patients with transient neonatal diabetes and submicroscopic chromosome 6 duplications were investigated. The duplications were confirmed by microsatellite analysis and subsequently mapped using tiled chromosome 6 array Comparative Genomic Hybridisation (aCGH) and MLPA. Duplication boundaries were compared to identify the minimal shared region of duplication. These data were then used with available clinical data to identify associations between size of 6q24 duplication and severity of TND phenotype.

RESULTS: Alignment of the minimal region of duplication to the human genome reduced the minimal TND critical region, formerly estimated at 440 kb, to 160-173 kb, revealing PLAGL1 (pleiomorphic adenoma gene-like 1) and HYMAI (imprinted in hydatidiform mole) to be the only genes wholly included therein. Additionally, the complete paternal duplication of a region containing the theoretical protein FAM164B was associated with the severe growth restriction observed in 6q24 duplication patients.

CONCLUSIONS/INTERPRETATION: This study has significantly reduced the critical region associated with 6q24 TND. It has eliminated several previous TND candidate genes, leaving the overlapping imprinted genes PLAGL1 and HYMAI as the only remaining complete candidate genes for 6q24 TND. Moreover, these data provide the first evidence that an additional region, encompassing the theoretical protein FAM164B, may have a critical role in the growth restriction phenotype observed in many 6q24 TND patients.

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More information

Accepted/In Press date: 30 July 2010
Published date: November 2010
Organisations: Human Genetics

Identifiers

Local EPrints ID: 162271
URI: http://eprints.soton.ac.uk/id/eprint/162271
ISSN: 0012-186X
PURE UUID: bb82e721-acc5-4673-a252-f8a63398c990
ORCID for I.K. Temple: ORCID iD orcid.org/0000-0002-6045-1781
ORCID for D.J.G. Mackay: ORCID iD orcid.org/0000-0003-3088-4401

Catalogue record

Date deposited: 17 Aug 2010 16:22
Last modified: 05 Nov 2019 01:57

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