Tertiary structure prediction of the wildtype protein (left column) and with the mutants.

<p>3D structure was predicted at Protein Homology/analogY Recognition Engine (PhyreEngine) from the Structural Bioinformatics Group, Imperial College, London, at <a href="http:www.sbg.bio.ic.ac.uk/phyre~/" target="_blank">http:www.sbg.bio.ic.ac.uk/phyre~/</a>. The plain arrows show the changes in the shape of the protein between the wildtype and p.P384L.</p

Transactivation function of the variants of the MAMLD1 protein analyzed by the luciferase method.

<p>The activity is evaluated for pHes3-luc vector.</p

Incidence of exonic polymorphisms p.P359S and p.N662S, and relative haplotypes in normal controls and 46,XY DSD patients.

<p>Controls are combined with the published series (matched for ethnicity of patients and controls) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032505#pone.0032505-Kalfa1" target="_blank">[13]</a><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032505#pone.0032505-Chen1" target="_blank">[14]</a>. The χ-square test was performed. When combining all patients with the p.662G polymorphism whatever the p.359 allele, this p.662G was significantly more frequent in 46,XY DSD patients: 27.1% (n = 19) vs. 6.8% (n = 40), <i>p</i> = 0.0001.</p

Homology study showed that this amino acid was highly conserved through species for the c.1041C>A and c.1151C>T mutations.

<p>Homology study showed that this amino acid was highly conserved through species for the c.1041C>A and c.1151C>T mutations.</p

Clinical and hormonal data of patients with mutated <i>MAMLD1</i>.

<p>SD: standard deviation. ND: not determined. NA: not available. DHT: dihydrotestosterone. DHEA: dihydroepiandrsosterone. Parentheses indicate the standard deviation for height and weight and the normal range for hormone serum levels. Testes of 1–2 ml can be regarded as normal, as recently reported by Shibata et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032505#pone.0032505-Shibata1" target="_blank">[34]</a>.</p>*<p>It is notable that anti-mullerian hormone and inhibin were lowered in one case. <i>MAMLD1</i> is indeed reported to be expressed in Sertoli cells, as well <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032505#pone.0032505-Fukami1" target="_blank">[15]</a>.</p

Electrochromatograms and pedigrees of the three patients with <i>MAMLD1</i> mutations.

<p>The black squares indicate patients with posterior hypospadias. All mutant sequences were controlled by wildtype (WT) DNA. Regarding case 1's family, only the members III-3 and II-4 were genotyped, as the other members in the pedigree declined genetic testing.</p

Additional file 1 of Challenges in the care of individuals with severe primary insulin-like growth factor-I deficiency (SPIGFD): an international, multi-stakeholder perspective

Additional file 1: Title of data: GRIPP2 table of patient and public involvement*. Description: Table presenting the GRIPP2 checklist, reporting patient and public involvement

Image_2_Identifying patient-related predictors of permanent growth hormone deficiency.tiff

ObjectiveIsolated childhood growth hormone deficiency (GHD) can persist into adulthood, and re-testing at the transition period is needed to determine whether continued growth hormone therapy is indicated. Here, our objective was to identify predictors of permanent GHD.DesignRetrospective single-centre study of patients with childhood-onset GHD who were re-tested after adult height attainment.MethodsAuxological, clinical, laboratory, and MRI data throughout follow-up were collected.ResultsWe included 101 patients. At GH treatment initiation, age was 8.1 ± 0.4 years, height -2.25 ± 0.8, and BMI -0.27 ± 0.1 SDS. The 29 (28.7%) patients with persistent GHD had lower height SDS (-2.57 ± 0.1 vs. -2.11 ± 0.1, pConclusionsHeight <-3 SDS at GHD diagnosis and pituitary MRI abnormalities should lead to a high index of suspicion for persistent GHD.</p

Image_1_Identifying patient-related predictors of permanent growth hormone deficiency.tiff

ObjectiveIsolated childhood growth hormone deficiency (GHD) can persist into adulthood, and re-testing at the transition period is needed to determine whether continued growth hormone therapy is indicated. Here, our objective was to identify predictors of permanent GHD.DesignRetrospective single-centre study of patients with childhood-onset GHD who were re-tested after adult height attainment.MethodsAuxological, clinical, laboratory, and MRI data throughout follow-up were collected.ResultsWe included 101 patients. At GH treatment initiation, age was 8.1 ± 0.4 years, height -2.25 ± 0.8, and BMI -0.27 ± 0.1 SDS. The 29 (28.7%) patients with persistent GHD had lower height SDS (-2.57 ± 0.1 vs. -2.11 ± 0.1, pConclusionsHeight <-3 SDS at GHD diagnosis and pituitary MRI abnormalities should lead to a high index of suspicion for persistent GHD.</p

Number of mutations identified through the WES analysis of DNA sample from the PNDM patient.

<p>*<i>Novel</i>: a novel mutation means that it is not present in the public database dbSNP130 and the eight HapMap exomes sequenced by Ng et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0013630#pone.0013630-Ng1" target="_blank">[7]</a>.</p>†<p><i>Concordance</i>: % of similar allele assignment among exomic mutations detected on the Illumina Human1M-Duo array and those discovered by WES.</p>‡<p><i>Sensitivity</i>: % of exomic mutations present on the Illumina Human1M-Duo array that have been discovered by WES.</p