PMC3265394_01
The three studied Muslim-Arab pedigrees with GSIII. (A) All members of Pedigree 1 were heterozygous for MLPH (c.102C>T; p.R35W), except for the clinically diagnosed GSIII patient DB200, who is homozygous. (B) In Pedigree 2, DB214, DB247, DB248, and DB251 are heterozygous for (c.102C>T; p.R35W) while DB212, DB213, DB250 and DB252, all diagnosed clinically with GSIII, are homozygous. (C) In Pedigree 3, patients DB273 and DB275 are homozygous while DB274 is heterozygous for MLPH (c.102C>T; p.R35W).
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F1
The studied patients were part of three distinct highly consanguineous Muslim-Arab families (Figure 1), in which Griscelli syndrome was suspected by physicians who previously diagnosed Griscelli syndrome type II in a Muslim-Arab family.
Hair and skin phenotypes of GSIII patients. (A) Non-affected sibling of DB200 with dark hair and skin. GSIII patients DB200 (B), DB212 (C) and DB213 (D) with light pigmented skin and silvery-gray hair. (E) Control dark hair with evenly distributed pigment in the hair shaft. (F) Silvery-gray hair of a GSII patient with a RAB27A mutation showing pigment clumping in the hair shaft. (G) Silvery-gray hair of GSIII patient DB200 showing pigment clumps in the hair shaft.
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F2
Patient DB200 (Figure 2B) of Pedigree 1 was first referred to our clinic at the age of 4 years because of recurrent pneumonia but his immunological and neurological evaluation were normal. Upon visiting our clinic, abnormal pigmentation compared to his siblings (Figure 2A) was noticed, including silvery-gray hair, eyebrows, and eyelashes, which are typical clinical features for all three types of GS. Microscopic analysis of the silvery-gray hair from patients DB200 (Figure 2G) and DB212 (not shown) were comparable to silvery-gray hair from a previously described GS type II patient (Figure 2F) with reported mutations in RAB27A; irregular distributed pigment clumps were observed in both GSII and GSIII hairs (Figure 2F, G). Apart from hypopigmentation and silvery-gray hair, two patients from Pedigree 2, DB213 (Figure 2D) and DB250 (not shown) showed no other clinical features. However, two other patients of this highly consanguineous family, DB212 (Figure 2C) and DB252 (not shown), had additional clinical anomalies.