Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

X-chromosomaler familiärer Kleinwuchs

Der X-chromosomale familiäre Kleinwuchs ist eine pseudo-autosomal dominant vererbte Erkrankung, die auf der Haploinsuffizienz aufgrund einer Mutation in der pseudoautosomalen Region des X-Chromosoms beruht. Die Penetranz ist auch innerhalb einer Familie sehr variabel, so dass bei schwerster Ausprägung auch eine Dyschondrosteosis Leri-Weill auftreten kann.

Symptome

Wachstumsstörung
Der Kleinwuchs ist dysproportional mit Zeichen einer Mesomelie.
Dysmorphie
Die Skelettfehlbildungen sind mesomelisch. Typisch ist die Madlung Deformität des Handgelenks.

Gliederung

Kleinwuchs, SHOX-bedingt
Dyschondrosteosis Leri-Weill
Langer-Mesomelie
X-chromosomaler familiärer Kleinwuchs
SHOX
Y-chromosomaler familiärer Kleinwuchs

Referenzen:

1.

Rappold GA et al. (2002) Deletions of the homeobox gene SHOX (short stature homeobox) are an important cause of growth failure in children with short stature.

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2.

Morizio E et al. (2003) Deletion of the SHOX gene in patients with short stature of unknown cause.

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3.

Ogata T et al. (1992) Chromosomal localisation of a pseudoautosomal growth gene(s).

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4.

Ogata T et al. (1992) Short stature in a girl with a terminal Xp deletion distal to DXYS15: localisation of a growth gene(s) in the pseudoautosomal region.

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5.

Sabherwal N et al. (2007) Long-range conserved non-coding SHOX sequences regulate expression in developing chicken limb and are associated with short stature phenotypes in human patients.

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6.

Henke A et al. (1991) Deletions within the pseudoautosomal region help map three new markers and indicate a possible role of this region in linear growth.

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7.

Chen J et al. (2009) Enhancer deletions of the SHOX gene as a frequent cause of short stature: the essential role of a 250 kb downstream regulatory domain.

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8.

Ballabio A et al. (1989) Contiguous gene syndromes due to deletions in the distal short arm of the human X chromosome.

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9.

Zuffardi O et al. (1982) The role of Yp in sex determination: new evidence from X/Y translocations.

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10.

Ogata T et al. (1995) Short stature in a girl with partial monosomy of the pseudoautosomal region distal to DXYS15: further evidence for the assignment of the critical region for a pseudoautosomal growth gene(s).

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11.

Rao E et al. (1997) Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome.

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12.

Rao E et al. (1997) FISH-deletion mapping defines a 270-kb short stature critical interval in the pseudoautosomal region PAR1 on human sex chromosomes.

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13.

Ellison JW et al. (1997) PHOG, a candidate gene for involvement in the short stature of Turner syndrome.

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14.

Binder G et al. (2003) Auxology is a valuable instrument for the clinical diagnosis of SHOX haploinsufficiency in school-age children with unexplained short stature.

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15.

Deng HW et al. (2002) A whole-genome linkage scan suggests several genomic regions potentially containing QTLs underlying the variation of stature.

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16.

Blum WF et al. (2007) Growth hormone is effective in treatment of short stature associated with short stature homeobox-containing gene deficiency: Two-year results of a randomized, controlled, multicenter trial.

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17.

Shanske A et al. (1999) Deletion of the pseudoautosomal region in a male with a unique Y;13 translocation and short stature.

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18.

Benito-Sanz S et al. (2012) Identification of the first recurrent PAR1 deletion in Léri-Weill dyschondrosteosis and idiopathic short stature reveals the presence of a novel SHOX enhancer.

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