There is no significant genotype-phenotype correlation in 5α-RD2. Gonadal malignancy risk seems to be low. If genetic analysis is not available at the time of diagnosis, stimulated T/DHT ratio can be useful, especially if different cut-off values are utilized in accordance with the pubertal status.

Thinning in RNFL was detected in normal-looking discs of obese children, and this thinning negatively correlated with BMI SDS. Further studies including large series are needed to clarify whether obesity has an effect on RNFL thickness.

The CYP27B1 gene encodes 25-hydroxyvitamin D-1α-hydroxylase. Mutations of this gene cause vitamin D-dependent rickets type 1A (VDDR-IA, OMIM 264700), which is a rare autosomal recessive disorder. To investigate CYP27B1 mutations, we studied 8 patients from 7 unrelated families. All coding exons and intron-exon boundaries of CYP27B1 gene were amplified by PCR from peripheral leukocyte DNA and subsequently sequenced. Homozygous mutations in the CYP27B1 gene were found in all the patients and heterozygous mutations were present in their normal parents. One novel single nucleotide variation (SNV, c.1215 T>C, p.R379R in the last nucleotide of exon 7) and three novel mutations were identified:, a splice donor site mutation (c.1215+2T>A) in intron 7, a 16-bp deletion in exon 6 (c.1022-1037del16), and a 2-bp deletion in exon 5 (c.934_935delAC). Both c.1215 T>C and c.1215+2T>A were present together in homozygous form in two unrelated patients, and caused exon 7 skipping. However, c.1215 T>C alone has no effect on pre-mRNA splicing. The skipping of exon 7 resulted in a shift of downstream reading frame and a premature stop codon 57 amino acids from L380 (p.L380Afs*57). The intra-exon deletions of c.1022-1037del16 and c.934_935delAC also resulted in a frameshift and the creation of premature stop codons at p.T341Rfs*5, and p.T312Rfs*19, respectively, leading to the functional inactivation of the CYP27B1 gene. Clinically, all the patients required continued calcitriol treatment and the clinical presentations were consistent with the complete loss of vitamin D1α-hydroxylase activity. In conclusion, three novel mutations have been identified. All of them caused frameshift and truncated proteins. The silent c.1215 T>C SNV has no effect on pre-mRNA splicing and it is likely a novel SNP. The current study further expands the CYP27B1 mutation spectrum.

There was a decreased GC-IPL thickness in children with T1DM without DR, suggesting that T1DM has an early neurodegenerative effect on retinal ganglion cells that occurs when the vascular component of DR is absent. SD-OCT may be more useful than ophthalmoscopic evaluation for detecting the earlier retinal structural changes of diabetes. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:473-477.].

Introduction: Mutations of the human GNRH1 gene are an extremely rare cause of normosmic idiopathic hypogonadotropic hypogonadism (nIHH), with only 6 mutations so far described. Patients: As part of a larger study, families with IHH were screened for mutations in genes known to be associated with IHH. In family 1, a 15-year and 9-month-old boy first presented during infancy with micropenis and bilateral cryptorchidism. His pubic and axillary hair is at stage 4 and 2, respectively. His testes are 1 ml bilaterally, and his stretched penile length is 3.6 cm. In family 2, a 19-year and 2-month-old man was referred because of absence of secondary sexual characteristics. His 13-year and 8-month-old sister did not have any breast development. Results: In 3 patients from 2 independent families we identified GNRH1 mutations. In the proband from family 1, a homozygous 1-base deletion (c.87delA) leading to a frameshift mutation (p.G29GfsX12) was identified. In family 2, the affected siblings had a novel homozygous mutation of c.G92A leading to p.R31H. Conclusion: Both mutations in these families are located in the region encoding the decapeptide and in the loci where the mutations have been described before. Therefore, these areas can be considered as mutational hot spots, indicating priority for routine diagnostic gene mutation analysis.