[Analysis of clinical manifestations and genetic mutations in a child with Laron syndrome].
OBJECTIVE
To analyze clinical manifestations and gene mutations in a child with severe short stature, explore its molecular mechanism and further clarify the diagnostic procedure for short stature.


METHODS
We observed clinical characteristics of a patient with short stature and did diagnostic examinations, assessed the function of GH-IGF-1 axis, and surveyed its family members.Genomic DNA was extracted from peripheral blood, GHR, IGFALS, STAT5b and GH1 gene were amplified by PCR for sequencing, including exons and splicing areas.


RESULTS
The patient presented symmetrical short stature (height -8.2 SDS) and facial features, and other congenital abnormalities.It displayed non-growth hormone deficiency. The baseline value of GH was 21 µg/L, and the peak was 57.9 µg/L. The value of IGF-1 was less than 25 µg/L, and the IGFBP-3 less than 50 µg/L. And IGF-1 generation test showed no response. There was no similar patients in the family members.Sequencing of GHR in the patient revealed a homozygous point mutation (c.Ivs6+1G>A), and her father and mother had the same heterozygous mutation. The same mutation was not identified for her sister.No other candidate gene was found.


CONCLUSIONS
As the result of combined clinical characteristics and lab examinations, as well as gene detection, the case was diagnosed with Laron syndrome and GHR gene mutation is the molecular mechanism.We should explicit the etiological diagnosis for short stature, and avoid missed diagnosis and misdiagnosis.
Department of Pediatrics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Guo-ying
GY
Chang
Shao-ke
SK
Chen
Email: gu_xuefan@163.com.
Xue-fan
XF
Gu
Zhu-wen
ZW
Gong
Qi-gang
QG
Zhang
D001483:Base Sequence; D001827:Body Height; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons; D006130:Growth Disorders / Q000097:blood / Q000235:genetics* / Q000473:pathology; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D046150:Laron Syndrome / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011986:Receptors, Somatotropin / Q000235:genetics*; D050799:STAT5 Transcription Factor / Q000235:genetics
D018972:Insulin-Like Growth Factor Binding Protein 3; D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I