A 17-year-old girl was referred to our endocrinology clinic for hyperkeratotic and pigmented lesions on her neck and whole trunk, which initially appeared when she was 4 years old. Her height was within the normal range during childhood (< 4 years) but gradually began to be under the normal growth curve, ultimately resulting in grown-up short stature. The patient was the first child of an unrelated Chinese couple. Her mother underwent vaginal delivery after a full-term pregnancy. The birth weight of the girl was 4 kg and the birth length was 50 cm. She exhibited no neurological defects or skeletal abnormalities, no diabetes mellitus or its related symptoms, and no family history of cancer. The patient’s parents, younger sister and brother had no significant medical history. On physical examination, the patient exhibited extensive, velvety, thick, hyperpigmented plaques involving the neck, back, and axillae. The patient was a non-dysmorphic girl with the height of 146 cm (<-2SD). Laboratory tests revealed no abnormal biochemical findings. The thyroid hormone, cortisol and androgen levels were within the normal range (the testosterone level demonstrated in Table was under the reference range, we tested testosterone one more time, and the other value was normal: 31.8 ng/dl). Fasting blood glucose and fasting insulin level were 88.2 mg/dL and 13.78μU/ml, respectively. The homeostasis assessment index for insulin resistance (HOMA-IR) as the outcome of the fasting insulin (mUI/ml) × glucose (mmol/l) /22.5 was 3.0. This result indicated no insulin resistance. These findings excluded the diagnosis of insulin resistance, T2D, Cushing’s syndrome and hyperandrogenism. X-ray examination (done at 14 years old) revealed no abnormalities. As genetic mutations have been recognized in several cases of syndromic AN, a mutational analysis was performed in the proband and parents. Written informed consent was signed by the proband and her parents. Peripheral blood samples (4 ml) of the proband and her parents were collected. Genomic DNA was extracted from the blood using a QIAamp DNA Mini Kit (Qiagen China Co., Ltd., Shanghai, China) according to the manufacturer’s recommendations. We first performed whole exome sequencing for the proband. Next, based on the test results of whole exome sequencing, the presence of the mutation in the proband and her parents was confirmed with direct Sanger sequencing of the affected exon. All coding exons were enriched using the xGen Exome Research Panel v1.0 (Integrated DNA Technology, Inc). Captured DNA libraries were sequenced on Illumina Hiseq X Ten according to the manufacturer’s instructions for paired-end 150 bp reads. Variants were considered as pathogenic mutations if they exhibited the following components: i) rare or absent in the above genome databases; ii) variation expected to have a drastic effect on the protein (nonsense mutation, frame shift mutation, mutation at a splice site, or missense mutation is highly conserved among species); and iii) variation predicted to be damaging. Sanger sequencing of the affected exon in FGFR3 was performed on DNA samples from the proband and her parents. According to the DNA sequence of the FGFR3 gene, primers of exon 14 of FGFR3 were designed using Primer Premier 5 software. The functional effects of protein variants were predicted by PolyPhen2 (/), SIFT () and Mutation Taster (). Through data mining, combined with genetic characteristics and clinical manifestations, we identified a heterozygous c.1949A > C, p.Lys650Thr mutation in FGFR3 of the proband, which is considered to be a pathogenic mutation. As the proband’s parents did not carry the mutation, the mutation identified in the proband was a de novo mutation. Sanger sequencing confirmation is shown in Fig.. The mutation caused change in the protein from K to T at p. Lys650, which is located in exon 14 of FGFR3. The pathogenicity of the mutation on bone and skin has been previously reported [–] and was confirmed using 3 different software programmes (The expected score scales of the mutation from each software programme are shown in Additional file: Table S1): SIFT (0), PolyPhen-2 (1) and Mutation taster (disease-causing).