ASN540SER mutation is associated with a mild form of hypochondroplasia: a 7 years follow-up in an Italian boy.

[achondroplasia]

Skeletal dysplasias (SKD ) are genetic disorders that result in the abnormal development of part or all of the skeleton and are commonly associated with short stature . The most common SKDs that typically result in short stature include achondroplasia /hypochondroplasia (HCH ) both caused by different mutations in the same gene . HCH diagnosis is based on the clinical appearance during development and conventional X-ray findings . In about 70 % of patients , missense mutations in the gene coding for the fibroblast Growth Factor Receptor 3 (FGFR 3 ) affects the amino acid at position 540 , mostly resulting in the amino acid exchange N 540 K .Subjects with HCH , heterozygous for the N 540 K substitution are significantly more disproportionate than individuals without this mutation . We report the clinical and radiographic features of an Italian family with HCH with an unusual N 540 S mutation , inside the common mutation hot spot of this condition . This is the first case reported in Italy and the third in the literature . During a 7 -years -follow-up , the boy started the puberty at the age of 11 .3 years and the growth spurt was observed between 13 .7 and 14 .9 years (+ 9 .1 cm .).During pubertal development the sitting height (SDS ) improved from - 1 .5 to - 0 .6 and the subischial leg length (SDS ) progressed from - 2 .6 to - 3 .3 .At the age of 16 .7 year the standing height was 157 .6 cm ( - 2 .4 SDS ), testicular volume was 15 ml and bone age 16 .5 year . The present study and the other two cases reported in the literature stress the important role of the asn 540 site in the tyrosine kinase I domain in the pathogenesis of HCH and underline the importance that , in patients with HCH who do not have the common N 540 K mutation , sequence analysis of the tyrosine kinase I domain of FGFR 3 should be performed to exclude other changes in that region .

Diseases
Validation

Diseases presenting "first case" symptom

achondroplasia

adrenal incidentaloma

allergic bronchopulmonary aspergillosis

alpha-thalassemia

aniridia

aromatase deficiency

canavan disease

carcinoma of the gallbladder

child syndrome

cholangiocarcinoma

classical phenylketonuria

coats disease

cohen syndrome

congenital toxoplasmosis

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dentin dysplasia

dracunculiasis

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

esophageal adenocarcinoma

esophageal carcinoma

fabry disease

familial mediterranean fever

focal myositis

gm1 gangliosidosis

harlequin ichthyosis

hodgkin lymphoma, classical

homocystinuria without methylmalonic aciduria

junctional epidermolysis bullosa

kabuki syndrome

krabbe disease

lamellar ichthyosis

legionellosis

liposarcoma

locked-in syndrome

malignant atrophic papulosis

monosomy 21

neonatal adrenoleukodystrophy

oculocutaneous albinism

omenn syndrome

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

primary hyperoxaluria type 1

proteus syndrome

pyomyositis

systemic capillary leak syndrome

thoracic outlet syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

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